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Nutritional Research May Be Useful in Treating Tendon Injuries

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Elsevier Editorial System(tm) for Nutrition
Manuscript Draft
Manuscript Number: NUT-D-15-00641R1
Title: Nutritional Research May Be Useful in treating Tendon Injuries.
Article Type: Review
Keywords: Nutrition, Tendon, Tenocytes, Achilles tendon, rotator cuff,
Collagen, Proteoglycans, Vitamins C & E, Zinc, Manganese, Copper,
Leucine, Arginine, Glutamine
Corresponding Author: Dr. Luke Theodore Curtis, MD
Corresponding Author's Institution: Curtis Research
First Author: Luke Theodore Curtis, MD
Order of Authors: Luke Theodore Curtis, MD
Abstract: Tendon injures cause a huge amount of disability, pain, and
medical costs. However, relatively little is known about tendon biology
and healing. Many tendon related surgical procures are not very
successful and leave the patient with essentially a chronic injury. New
therapeutic approaches for tendon injury are needed. Preliminary
evidence suggests that various nutrients such as protein, amino acids
(leucine, arginine, glutamine), vitamins C+D, manganese, copper, zinc,
and phytochemicals may be useful to improve tendon growth and healing.
Much more research on nutrition and tendon health is needed. Since many
nutrients are required for tendon health, nutritional interventions
involving multiple nutrients may be more effective than single nutrient
strategies. In the future, ideal treatment regimens for tendon injuries
may include a multifaceted "bundle" of nutrition, drugs, biological
products, extracellular matrix therapies, exercise/ [physical therapy,
and possibly surgery.
11-12-2015
Dear Dr. Undurti Das
Thanks for your review and helpful comments from the reviewers. I have tried
to best address the reviewers questions in the new review paper submitted.
Where I made changes I mentioned them in the review document comments in
Word. My responses to the comments of the reviewers are listed below inside
the @@ @@.
Thanks for your time and editorial consideration. I hope you have space and
interest for this article. I would be happy to make more revisions if you wish. I
hope this short review will stimulate more clinical and research interest in
nutrition and tendon health.
Luke Curtis MD, MS, CIH
12570 Portland Avenue South #223
Burnsville, MN 55337 USA
H 952-513-7568
C 847-769-4768
LukeTCurtis@aol.com
Ms. Ref. No.: NUT-D-15-00641
Title: Nutritional Research May Be Useful in
treating Tendon Injuries.
Nutrition
Dear Dr. Curtis,
Your article
Nutritional Research May Be Useful in treating Tendon Injuries. has been
returned by our reviewers. In its present form, it cannot be accepted for
publication in Nutrition.
However, Nutrition would be willing to reconsider
Cover Letter
it for possible publication, if you feel you can fully address the reviewers'
comments. Please remember that we would have to send your revised
manuscript
back to the original referees and keep this time frame in mind when you
respond
to the critiques.
If you wish to have your manuscript reconsidered for
publication, please revise it and return it to this office by 2015-12-09
00:00:00.
For your guidance, reviewers' comments are appended
below.
Please provide along with your cover letter a list of your responses
to the reviewers' critiques and the changes you have made in your manuscript.
To submit a revision,
please go to http://ees.elsevier.com/nut/ and login as an Author. On your
Main
Menu page is a folder entitled "Submissions Needing Revision". You will find
your submission record there.
Your username is: LukeTCurtis@aol.com
If
you need to retrieve password details please go to:
http://ees.elsevier.com/nut/automail_query.asp
We look forward to hearing from you.
Yours
sincerely,
Undurti N. Das, M.D., FAMS, FRSC
Review
Editor
Nutrition
Reviewers' comments:
Reviewer #1: Major comments:
1.
The review article usually needs at least one figure or table for
illustration. @@ Good point. I have included a table that summarizes data on
which nutrients may be helpful in human, animal, cell culture studies. If you
think this table is redundant we could skip it. @@
2. There is no any keyword for the abstract. @@ I have added some keywords-
thanks for catching my error@@
Minor
comments:
1. There is no line number for the text. @@ Good idea- I added them. @@
2. There are a few
typographic errors in the last line on page 1 and the 14th line on page 5.
3. @@ Corrected- thank you @@
There is lack of journal names for reference # 7 and # 27. @@ Thanks sorry for
my silly errors@@
Reviewer #2:
This review attempts to highlight a paucity of human research regarding the
influence of nutrition on connective tissue healing. This review does highlight
the lack of human research by presenting almost exclusively animal studies;
however, does not make a strong case for urging clinicians to "consider
nutritional approaches in as a partial strategy in treating tendon problems" as
stated in the Purpose. It well known that not all animal research translates to
human research and there should be extensive human research before any
clinical
recommendations should be made. @@ I have included a statement in the
conclusions that “Most of the research on tendons and nutrition have dealt
with animal or cell culture studies which may or may not be representative of
the effects of nutrition and tendon health in humans.
@@
If you wish I could discuss this further.
Abstract
-change "procures" to
"procedures" @@ Corrected- thank you@@
-remove"[" symbol before "physical
therapy"
Introduction
Paragraph 1, Line 4-Please clarify the annual cost. It
is presented here in Euros but your research institute is located in the US, are
you speaking to the annual cost in the US or International? @@ Mentioned US$
cost of about US$$196 Billion)
Comment [LC1]: Additional testing
in humans is needed.
Methods
P1,
L5-Change "FDA. Gov" to "FDA.gov" @@Yes-thanks good catch@@
P1, L13-Provide exact number of research
articles and exact number of reviews (out of the approx. 110 total collected)
that were actually selected for citation based on your criteria
provided.
Nutrition and Tendon Growth and Healing
P1, L5-Please clarify
whether increases in tendon CSA were due to whey protein supplementation or
RT
or to both concurrently. @@ I mentioned concurrent whey protein and exercsise
P1, L6-Should say "grams per day" (CVhanged- thanks@@
P2, L2-Change
"intervention's" to "interventions" @@ Corrected@@
P2, L16-Pathway name is mTOR not TOR @@ Corrected @@
P2,
L19-Remove "bodyweight" as "mass" applies to both muscle and lean that you
are
referring to. @@ good catch@@
P2, L20-Replace "muscle-wasted" with "cachectic" as this is the
preferred term for disease-related muscle wasting @@ OK- although loss of
muscle mass is often a combination of cachectia and sarcopenia. @@
P3, L7-Replace "had" with
"with" @@ Fixed@@
Reviewer #1: Major comments:
1.
The review article usually needs at least one figure or table for
illustration. @@ Good point. I have included a table that summarizes data on
which nutrients may be helpful in human, animal, cell culture studies. If you
think this table is redundant we could skip it. @@
2. There is no any keyword for the abstract. @@ I have added some keywords-
thanks for catching my error@@
Minor
comments:
1. There is no line number for the text. @@ Good idea- I added them. @@
2. There are a few
typographic errors in the last line on page 1 and the 14th line on page 5.
3. @@ Corrected- thank you @@
There is lack of journal names for reference # 7 and # 27. @@ Thanks sorry for
my silly errors@@
Reviewer #2:
This review attempts to highlight a paucity of human research regarding the
influence of nutrition on connective tissue healing. This review does highlight
the lack of human research by presenting almost exclusively animal studies;
however, does not make a strong case for urging clinicians to "consider
nutritional approaches in as a partial strategy in treating tendon problems" as
stated in the Purpose. It well known that not all animal research translates to
human research and there should be extensive human research before any
clinical
recommendations should be made. @@ I have included a statement in the
conclusions that “Most of the research on tendons and nutrition have dealt
with animal or cell culture studies which may or may not be representative of
the effects of nutrition and tendon health in humans.
@@
If you wish I could discuss this further.
Abstract
-change "procures" to
"procedures" @@ Corrected- thank you@@
-remove"[" symbol before "physical
therapy"
Introduction
Paragraph 1, Line 4-Please clarify the annual cost. It
is presented here in Euros but your research institute is located in the US, are
Comment [LC1]: Additional testing
in humans is needed.
*Response to Reviewers
you speaking to the annual cost in the US or International? @@ Mentioned US$
cost of about US$$196 Billion)
Methods
P1,
L5-Change "FDA. Gov" to "FDA.gov" @@Yes-thanks good catch@@
P1, L13-Provide exact number of research
articles and exact number of reviews (out of the approx. 110 total collected)
that were actually selected for citation based on your criteria
provided.
Nutrition and Tendon Growth and Healing
P1, L5-Please clarify
whether increases in tendon CSA were due to whey protein supplementation or
RT
or to both concurrently. @@ I mentioned concurrent whey protein and exercsise
P1, L6-Should say "grams per day" (CVhanged- thanks@@
P2, L2-Change
"intervention's" to "interventions" @@ Corrected@@
P2, L16-Pathway name is mTOR not TOR @@ Corrected @@
P2,
L19-Remove "bodyweight" as "mass" applies to both muscle and lean that you
are
referring to. @@ good catch@@
P2, L20-Replace "muscle-wasted" with "cachectic" as this is the
preferred term for disease-related muscle wasting @@ OK- although loss of
muscle mass is often a combination of cachectia and sarcopenia. @@
P3, L7-Replace "had" with
"with" @@ Fixed@@
Bullet Points- Nutritional Research May be Useful in Treating Tendon Injuries.
Tendon Injuries Cause a Huge Amount of Pain, Disability, Medical Costs, and Suffering.
Tendon injuries are hard to treat
Relatively little is known about tendon biology as compared to muscle or bone biology.
Limited Research Suggests Nutritional Treatments May Be Useful for Tendon Healing
Amino acids, vitamins D&C, manganese, copper, and zinc may be useful for tendon healing.
*Highlights (for review)
1
1
NUTRITIONAL RESEARCH MAY BE USEFUL IN TREATING TENDON INJURIES 2
Luke Curtis, MD, MS, Curtis Research, 12570 Portland Avenue S #223, 3
Burnsville, MN 55337, USA LukeTCurtis@aol.com 4
5
Abstract 6
Tendon injures cause a huge amount of disability, pain, and medical costs. 7
However, relatively little is known about tendon biology and healing. Many 8
tendon related surgical procedures are not very successful and leave the 9
patient with essentially a chronic injury. New therapeutic approaches for 10
tendon injury are needed. Preliminary evidence suggests that various 11
nutrients such as protein, amino acids (leucine, arginine, glutamine), vitamins 12
C+D, manganese, copper, zinc, and phytochemicals may be useful to improve 13
tendon growth and healing. 14
Much more research on nutrition and tendon health is needed. Since many 15
nutrients are required for tendon health, nutritional interventions involving 16
multiple nutrients may be more effective than single nutrient strategies. In the 17
future, ideal treatment regimens for tendon injuries may include a multifaceted 18
“bundle” of nutrition, drugs, biological products, extracellular matrix therapies, 19
exercise/ physical therapy, and possibly surgery. 20
Comment [LC1]: Corrected
*Manuscript
Click here to view linked References
2
21
Keywords: tendon, Achilles tendon, rotator cuff, tenocytes, vitamin C, amino 22
acids, manganese, copper, zinc, phytochemicals. 23
24
Introduction 25
Tendon injuries cause a great deal of pain, disability, and medical & economic 26
costs [1, 2]. The exact prevalence of tendon injuries is unknown, but it is 27
estimated that worldwide over 30 million patients have tendon-related surgical 28
procedures annually at a medical cost of over €140 billion per year (about US$ 29
196 Billion) [3]. Surgical repairs for tendon injuries require a long and painful 30
recuperation and are often not very successful, leaving the patient with 31
essentially a permanent injury [3-7]. Clearly, better treatments for tendon 32
injuries are needed. 33
Tendon healing is generally a very slow and incomplete process [1, 6-8]. Use of 34
biological and biomaterial approaches, such as use of platelet rich plasma, 35
extracellular matrix (ECM)/ scaffold treatments, regulation of growth factors 36
and cytokines, and stem cell based approaches, potentially offer promise in 37
speeding up and improving repair of torn or otherwise damaged tendons [1, 3, 38
5, 8, 9]. There is a dearth of both basic and applied tendon research, and our 39
basic understanding of tendon biology lags far behind that of muscle or bone 40
[1, 2, 6, 7] . 41
Comment [LC2]: Added this
3
The purpose of this short review is twofold: 1) To describe existing research on 42
nutrition and tendon health/ healing and: 2) To stimulate interest in clinicians 43
and researchers to consider nutritional approaches as a partial strategy in 44
treating tendon problems. 45
46
Methods 47
About 110 research and review articles were collected for information about for 48
studies relating tendons with nutrition and related topics. Animal and cell 49
culture studies were included as in vivo studies of nutrition and tendons in 50
humans is currently sparse. Various Medical Database were searched for 51
articles include PubMed, Google and Google Scholar, FDA.Gov, and clinical 52
trials.gov. No time restriction was placed on the search. Searched terms 53
included a variety of tendon related terms including tendon, tendonitis, tendon 54
tears, Achilles tendon, rotator cuff, patellar tendon, tenocytes, collagen, leucine 55
rich proteins, and proteoglycans. Many nutritional related terms were also 56
used including calories, omega 3 fats, protein, amino acids (such as leucine, 57
glutamine, arginine and taurine), fruits, vegetables, phytochemicals, vitamins 58
(including all of the various vitamins), minerals (Ca, Mg, Zn, Cu, Mn, Fe, Mo, 59
Si) and coenzyme Q10. A total of 33 articles were selected for citing in this 60
review if they were deemed to have relevance in exploring relationships between 61
tendons and nutrition. 62
Comment [LC3]: Corrected
Comment [LC4]: Added0 change if
you add more references
4
63
Nutrition and Tendon Growth and Healing 64
Nutrition may play a major role in tendon healing, although research has been 65
sparse to date. The majority of work to date has involved animals or cultured 66
human cells, although there are a few clinical human studies. Some animal 67
and human studies report significantly better tendon growth or collagen 68
synthesis following various nutritional interventions. Supplementation with 69
19.5 grams per day of whey protein was found to significantly increase patellar 70
and quadricep tendon cross sectional area in a group of 22 young men 71
concurrently in an exercise program [10]. Vitamin C is necessary for the 72
enzymatic synthesis of both collagen proteins and several proteoglycans found 73
in tendons [11]. Vitamin C is also a transcriptional promoter of collagen 74
synthesis [12]. A rat study reported that high dose oral vitamin C 75
supplementation significantly accelerated healing of ruptured Achilles tendons 76
[12]. Another rat study reported that a vitamin D deficient diet significantly 77
slowed healing and buildup of biomechanical strength of the rotator cuff [13]. 78
High dose oral glucosamine/ chondroitin sulphate was found to significantly 79
accelerate tendon to bone healing in rabbits [14]. Taurine injected at the 80
tendon repair site was found to significantly improve load strength in rats with 81
repaired Achilles tendons [15]. Deficiencies of biotin, folate, or manganese 82
were found to significantly increase tenosynovitis in reovirus infected chickens 83
[16].
84
Comment [LC5]: Added
Comment [LC6]: Added
5
Since collagen forms the major extracellular protein in tendons, muscle, and 85
ligaments [1, 11, 17] dietary interventions to increase collagen synthesis 86
and/or protein synthesis in general may be helpful in rebuilding tendons. 87
Such dietary interventions might include providing sufficient overall calories/ 88
protein and supplementation with such nutrients as trace minerals and/or 89
amino acids. Numerous animal and human studies have reported that diets 90
deficient in protein and/or calories lead to significantly less collagen 91
production [11]. Many trace minerals such as zinc, copper, and manganese 92
play a key role in collagen metabolism, and nutritional deficiencies in these 93
minerals have been linked to poorer collagen synthesis [18, 19]. Amino acid 94
supplementation with glutamine, arginine, and branched chained amino acids 95
(leucine, isoleucine, and valine) was found to significantly increase skin 96
collagen synthesis in UV-irradiated mice [20]. Various studies have reported 97
that dietary consumption of leucine or its metabolite ß-hydroxy-ß-98
methylbutyrate (HMB) simulate protein synthesis via signaling pathways 99
involving mmTOR(mammalian target of rapamycin) in a doseresponse manner 100
[21]. Other studies have reported that oral supplementation of mixtures of 101
HMB, glutamine, and arginine can significantly increase muscle and/or lean 102
mass in a wide variety of patients including the elderly [22], cachectic HIV 103
patients [23], and muscle-wasted cancer patients [24]. . 104
Since many nutrients are involved with tendon and collagen metabolism, 105
nutritional interventions employing multiple nutrients may yield better results 106
Comment [LC7]: Change β to beta??
Comment [LC8]: Add m thanks for
the correction
Comment [LC9]: Removed
bodyweight.
Comment [LC10]: Changed
6
as compared to studies employing only one nutrient. A human study of 90 107
patients with rotator cuff surgery reported that the use of a multifaceted 108
Tenosan® supplement containing 1 gram of arginine l-alpha- ketoglutarate, 1.1 109
grams methylsulfonylmethane, 600 mg hydrolyzed collagen, 120 mg. vitamin 110
C, and 100 mg bromelain daily was associated with significantly better repair 111
integrity at final follow-up [25]. A human study of patients with insertional 112
Achilles tendinopathy treated 32 patients with the Tenosan supplement 113
(mentioned above) and 32 patients with placebo. All patients also underwent 3 114
courses of extracorporeal shockwave therapy. After 6 months pain was 115
significantly reduced and patient satisfaction was significantly increased in the 116
Tenosan treated patients as compared to the placebo treated patients [26]. 117
In vitro studies also suggest that various nutrients like phytochemicals from 118
plants or Ω-3 fats may be useful for tendon repair and health. Cyanidin is a 119
colored pigment found in many fruits and vegetables including red cabbage, 120
cherries, bilberries, serviceberries, red and black grapes, blueberries, and 121
blackberries. Cyanidin (100 µg/ml) was found to inhibit autophagic cell death 122
in human rotator cuff tenoblasts [27]. Curcumin (a diarylheptanoid found in 123
turmeric) was found to significantly reduce inflammation in human tenocytes 124
[28]. A study of Achilles tendons from orofloxicin treated rats reported that 125
degenerative changes were significantly more common in rats fed a magnesium 126
deficient diet as compared to a magnesium sufficient diet [29]. A supplement 127
containing vitamin C, collagen type 1, manganese, and mucopolysaccharides 128
Comment [LC11]: Thanks for
catching my error.
7
showed significant anti-inflammatory and anti-catabolic effects of human 129
tenocytes in vitro [30] . The Ω-3 fatty acid EPA (eicospentaenoic acid) was 130
found to enhance collagen formation in cultured human medial collateral 131
ligament fibroblasts [31] . 132
Proteoglycans are proteins found in the tendons’ extracellular matrix (ECM) 133
which play a critical role in the function and structure of tendons. The two 134
main classes of tendon proteoglycans include: 1) small leucine rich 135
proteoglycans (SLRPs) including decorin, fibromodulin, lumican, and biglycan; 136
137
these proteins bind to collagen fibrils and 2) large molecular proteoglycans 138
such as aggrecan and versican which are associated with tendon loading and 139
mobilization [32, 33]. Perhaps nutritional interventions with leucine and/or 140
other nutrients may improve synthesis and function of tendon proteoglycans. 141
Understanding of the relationships between nutrition and tendon proteoglycans 142
is lacking and major research in this area is clearly needed. 143
SUMMARY 144
Table 1 below summarizes various human, animal and cell culture studies 145
which suggest that various nutrients may be helpful to tendon health, growth 146
or repair. 147
148
Comment [LC12]: Perhaps a
summary table would be good to
include here. If no- it could easily
beremoved.{Farup, 2014 #153}
8
Table 1- Human, Animal, and Cell Culture Studies which Suggest the
Following Nutrients May be Helpful in Tendon Health, Growth, and Repair
and/or Collagen Synthesis. Numbers listed refer to references.
Nutrient
Human
Studies
Animal Studies-
Mammals or Birds
Cell Culture
Studies or
Animal
Organs
Whey Protein
[10]
Vitamin C
[12]
Vitamin D
[13]
Glucosamine /
Chondroitin Sulfate
[14]
Taurine
[15]
Biotin, Folate, Manganese
[16]
Calories
[11]
[11]
Protein
[11]
[11]
Glutamine, Arginine,
Leucine, Isoleucine,
Valine
[20]
Tenosan®. 1 gram of
arginine l-alpha-
ketoglutarate, 1.1 grams
methylsulfonylmethane,
600 mg hydrolyzed
collagen, 120 mg. vitamin
C, and 100 mg bromelain
daily.
[25, 26]
Cyanadin (Phytochemical
found in many fruits/
vegetables)
[27]
Curcumin
[28]
Magnesium
[29]
Vitamin C, Collagen Type
[30]
9
Table 1- Human, Animal, and Cell Culture Studies which Suggest the
Following Nutrients May be Helpful in Tendon Health, Growth, and Repair
and/or Collagen Synthesis. Numbers listed refer to references.
Nutrient
Human
Studies
Animal Studies-
Mammals or Birds
Cell Culture
Studies or
Animal
Organs
1, Manganese, &
Mucopolysaccharides
EPA or Eicospentaenoic
Acid (-3 Fatty Acid)
[31]
149
CONCLUSION 150
Much more research and clinical attention is needed to develop better 151
treatment strategies for torn or damaged tendons. Most of the research on 152
tendons and nutrition have dealt with animal or cell culture studies which may 153
or may not be representative of the effects of nutrition and tendon health in 154
humans. Additional research on human nutrition and tendon health/repair is 155
needed. Most nutritional interventions interventions are fairly inexpensive and 156
have a low risk of side effects. A “bundle” of multiple interventions may be 157
needed for optimal tendon growth and healing. In the future, ideal treatment 158
for tendon injuries may include a multifaceted program of good nutrition/ 159
supplements, drugs, biological products/ stem cells, extracellular matrix/ 160
scaffold therapies, exercise/ physical therapy, and possibly surgery. 161
REFERENCES 162
Comment [LC13]: Additional testing
in humans is needed.
10
163
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11
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286(32):28556-28566. 231
29. Shakibaei M PK, Schwabe R, Vormann J, Stahlman R: Ultrastructure of Achilles tendomn of rats 232
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... Since TP is characterized by irregular or disturbed homeostasis, poor nutrition can lead to the development of this disease [3]. However, adequate food intake of both macro-and micronutrients may be a plausible strategy in the prevention and amelioration of the disease, with potential benefits of nutrition on tendon health emerging [10]. It is necessary to understand the effect of the interaction of these substances with cell and tissue biology and, thus, use nutritional management as a unique tool towards the treatment of TP [11,12]. ...
... Recent findings have demonstrated that glucose metabolism is disturbed during injury and recovery in TP in both humans and mice [10]. These changes include increases in glucose, lactate, and pyruvate contents in healing human Achilles tendons [10] and stimulation of glycolysis, lactate synthesis, and TCA cycle in injured mouse Achilles tendons [11]. ...
... Recent findings have demonstrated that glucose metabolism is disturbed during injury and recovery in TP in both humans and mice [10]. These changes include increases in glucose, lactate, and pyruvate contents in healing human Achilles tendons [10] and stimulation of glycolysis, lactate synthesis, and TCA cycle in injured mouse Achilles tendons [11]. The lower T-HK activity found in the MA and AA groups in Phase II may be because the function of T-HK is to phosphorylate glucose using ATP to form glucose-6-phosphate [24]. ...
Article
Full-text available
Tendinopathy (TP) is a complex clinical syndrome characterized by local inflammation, pain in the affected area, and loss of performance, preceded by tendon injury. The disease develops in three phases: Inflammatory phase, proliferative phase, and remodeling phase. There are currently no proven treatments for early reversal of this type of injury. However, the metabolic pathways of the transition metabolism, which are necessary for the proper functioning of the organism, are known. These metabolic pathways can be modified by a number of external factors, such as nutritional supplements. In this study, the modulatory effect of four dietary supplements, maslinic acid (MA), hydroxytyrosol (HT), glycine, and aspartate (AA), on hepatic intermediary metabolism was observed in Wistar rats with induced tendinopathy at different stages of the disease. Induced tendinopathy in rats produces alterations in the liver intermediary metabolism. Nutraceutical treatments modify the intermediary metabolism in the different phases of tendinopathy, so AA treatment produced a decrease in carbohydrate metabolism. In lipid metabolism, MA and AA caused a decrease in lipogenesis at the tendinopathy and increased fatty acid oxidation. In protein metabolism, MA treatment increased GDH and AST activity; HT decreased ALT activity; and the AA treatment does not cause any alteration. Use of nutritional supplements of diet could help to regulate the intermediary metabolism in the TP.
... Several factors have been reported to be associated with better outcomes after operative treatment of RC, including age [7], stiffness [8], gender [9], fatty infiltration [10], tear size [11], and comorbidities [12]. Although various nutrients, such as proteins, amino acids (leucine, arginine, glutamine), vitamins C and D, manganese, copper, zinc, and phytochemicals, have also been suggested to contribute to improving RC tendon growth and healing [13], less preliminary evidence supports the idea that they influence the postoperative recovery of RC repair. Gumina et al. showed the long-term effectiveness of hydrolyzed collagen, methylsulfonyl-methane, and arginine for pain reduction in patients after RC repair [14]. ...
... With the increase in research in recent years, various adjuvant strategies and postoperative measures improving the surgical outcomes in RC injury have been suggested [7][8][9][10][11][12]. Among these measures, the administration of some nutritional or dietary supplements was reported to benefit postoperative recovery [13,25,26]. For example, increasing dietary protein may be beneficial after an injury, in terms of both attenuating muscle atrophy and promoting repair [27]. ...
... Despite the lack of direct evidence supporting the idea that dietary factors affect rotator cuff recovery in previous reports, numerous studies have proven that dietary habits and supplement intake could regulate tendon health [13,25,26]. Since tendon impairment is one of the major causes of RC injury and tendon health is required for the process of RC recovery [31,32], dietary elements and habits associated with tendon health may also be critical for RC healing. ...
Article
Full-text available
Some nutritional factors have been suggested to improve postoperative outcomes in rotator cuff (RC) repair, but dietary effects on the recovery speed after the surgery remain undefined. To investigate the potential roles of dietary habits in this context, we analyzed the 12-month follow-up data of 55 patients with RC repair and found that these patients could be categorized into a rapid recovery group (n = 35) and slow recovery group (n = 20) according to their postoperative recovery patterns. Group-based logistic analysis revealed that habitual intakes of meat (OR = 1.84, 95%CI, 1.22–2.76, p = 0.003), fruits (OR = 2.33, 95%CI, 1.26–5.67, p = 0.01), and wheat-flour foods (OR = 1.62, 95%CI, 1.2–2.25, p = 0.002) were significantly associated with rapid recovery. Moreover, among all intakes of wheat-flour foods, intakes of steamed and boiled flour products were also associated with rapid recovery. Further mediation analysis showed that eosinophilic granulocytes (EOs) significantly mediated the association between rapid RC recovery and the habitual intakes of meat (mediation proportion = 17.5%, P-mediation < 0.0001), fruits (17.9%, p < 0.0001), and wheat-flour foods (11.4%, p < 0.0001). Thus, our study suggests that certain dietary habits play beneficial roles in the context of postoperative recovery for RC repair.
... Nutrition and diet may also have a role in the healing of the tendon after rupture. There are few studies addressing proper nutrition or supplementation following tendon injury (Curtis, 2016). Vitamin C is a promoter of collagen synthesis, and is necessary for the enzymatic synthesis of both collagen proteins and tendons proteoglycans (Berg & Kerr, 1992;Curtis, 2016). ...
... There are few studies addressing proper nutrition or supplementation following tendon injury (Curtis, 2016). Vitamin C is a promoter of collagen synthesis, and is necessary for the enzymatic synthesis of both collagen proteins and tendons proteoglycans (Berg & Kerr, 1992;Curtis, 2016). High dose of vitamin C supplementation in rats was found to promote early angiogenesis and increase the activity for procollagen-secreting fibroblasts and overall type I collagen production (Ömeroğlu et al., 2009). ...
Thesis
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Achilles tendon rupture (ATR) is a frequent and disabling injury. In the last decade the incidence of ATR has been increasing especially in middle aged men participating in recreational sports. Plantar flexion strength decrements and endurance impairments are observed in patients with ATR whether treated surgically or non-surgically. Factors associated with good recovery are yet to be determined, particularly in non-surgically treated patients. Therefore, the aim of this thesis was to examine Achilles tendon (AT) and triceps surae (TS) muscle-tendon unit biomechanics in non-surgically treated patients 1-year after ATR. The results show that after rupture, non-surgically treated tendons heal to an elongated length, accompanied by remodeling of the TS muscles to shorter fascicles, and a reduced muscle cross-sectional area. However, stiffness in the injured AT was not different compared to the contralateral limb 1-year after rupture, in contrast with previous studies done on surgically treated tendons around the same time point. The relative contribution of flexor hallucis longus (FHL) during submaximal plantarflexion was higher in the injured limb, and this appeared to compensate for the decreased medial gastrocnemius activity. The lengthening of the injured tendon was associated with greater relative FHL activity, lower stiffness, and worse patient-reported outcomes. It seems that the increased length of the tendon after rupture is responsible for the observed ob-jectively measured and self-reported functional deficits. Non-surgical treatment after ATR seems to allow the conservation of the displacement pattern in the ruptured tendon, suggesting that non-surgical treatment may preserve normal subtendon organization. However, displacement amplitude and non-uniformity were altered after rupture. Using selective electrical stimulation to scan for the representative areas of the TS subtendons within the cross section of the AT, the data indicates that lateral gastrocnemius subtendon was located in the most anterior region adjacent to medial gastrocnemius both in the healthy and ruptured, non-surgically treated tendon. The novel method devel-oped in this thesis enables individual assessment of the TS subtendon organi-zation within the AT and may enable patient-specific rehabilitation protocols in the future
... Certain animal and human studies have documented marked enhancements in tendon growth or collagen synthesis following diverse nutritional interventions. These include proteins and amino acids (like glycine, lysine, leucine, arginine, and glutamine), as well as vitamins C and D, alongside minerals such as manganese, copper, zinc, and phytochemicals [31][32][33]. Because the main protein in tendons is collagen, dietary treatments can be used to increase its synthesis, and, in addition, the synthesis of other proteins that aid tendon regeneration [34]. ...
... Thus, glucose metabolism is altered during tendon injury and subsequent recovery. These changes vary widely and include elevations in glucose, lactate, and pyruvate levels in healing human Achilles tendons [31] and stimulation of glycolysis, lactate synthesis, and pyruvate synthesis [27]. Similarly, to these authors, the results obtained in this research from the group with induced tendinopathy showed a clear tendency to increase glucose metabolism, which did not occur in the healthy group without induced tendinopathy. ...
Article
Full-text available
Achilles tendinopathy (TP) is characterized as the third most common disease of the musculoskeletal system, and occurs in three phases. There is currently no evidence of effective treatment for this medical condition. In this study, the modulatory effects of the minimally invasive technique intratissue percutaneous electrolysis (EPI) and combinations of EPI with four nutritional factors included in the diet, hydroxytyrosol (HT), maslinic acid (MA), glycine, and aspartate (AA), on hepatic intermediary metabolism was examined in Wistar rats with induced tendinopathy at various stages of TP. Results obtained showed that induced tendinopathy produced alterations in the liver intermediary metabolisms of the rats. Regarding carbohydrate metabolism, a reduction in the activity of pro-inflammatory enzymes in the later stages of TP was observed following treatment with EPI alone. Among the combined treatments using nutritional factors with EPI, HT+EPI and AA+EPI had the greatest effect on reducing inflammation in the late stages of TP. In terms of lipid metabolism, the HT+EPI and AA+EPI groups showed a decrease in lipogenesis. In protein metabolism, the HT+EPI group more effectively reduced the inflammatory effects of induced TP. Treatment with EPI combined with nutritional factors might help regulate intermediary metabolism in TP disease and reduce the inflammation process.
... β-alanine can increase muscle carnosine storage in skeletal muscle, offering protection against glycation and increasing calcium sensitivity (Donovan et al., 2012). Joint, tendon, and connective tissues are frequent injuries in combat athletes (Curtis, 2015). Fibrous tissues are essential in the connection between muscles and bones, providing the ability for combat athletes to perform various movements. ...
Book
This book informs readers and athletes of fundamental nutritional guidelines to enhance sport performance, and to reduce the likelihood of malnutrition and vulnerability to nutritional myths and concerns. It contains collected works from Sport and Exercise Studies scholars. The authors thoroughly researched numerous nutrition-related topics and their impact on sport performance and wrote chapters for this book aimed at providing suggestions and improvement strategies for athletes, coaches, health-educators, and other health and movement professionals – as well as any reader interested in improving their dietary choices and physical fitness. Topics discussed in this text include but are not limited to: plant-based diets, hydration and cutting water bloat, eating disorders, intermittent fasting, fat loss diets, ketogenic diets, juice cleanse, supplementation, the impact of social media, and more. Other than individuals simply wanting to better their diet and sport performance, those who will benefit from reading and applying this work include but are not limited to: (a) physical educators, (b) health educators, (c) coaches, (d) exercise instructors, (e) personal trainers, (f) physical and/or occupational therapists, and (g) nutritionists. This is a practical guide and overview of recommendations and suggestions written by practitioners for practitioners.
... These processes involve cellular migration and proliferation (figure 10b), enzymatic degradation of dysfunctional ECM components, and synthesis of new units of these components. All of them consume energy and nutrients [63], resulting in the formation of new blood vessels as a response/adaptation to the reparative processes. The cellular migration/infiltration behaviour, although could provide implications for cell-ECM interactions, was not examined in the in vitro study. ...
Article
Full-text available
The Ponseti method corrects a clubfoot by manipulation and casting which causes stress relaxation on the tendons. Here, we examined the effect of long-term stress relaxation on tendon extracellular matrix (ECM) by (1) an ex vivo stress relaxation test, (2) an in vitro tenocyte culture with stress relaxation and (3) an in vivo rabbit study. Time-dependent tendon lengthening and ECM alterations including crimp angle reduction and cleaved elastin were observed, which illustrated the mechanism of tissue lengthening behind the treatment-a material-based crimp angle reduction resulted from elastin cleavage. Additionally, in vitro and in vivo results observed restoration of these ECM alterations along with increased elastin level after 7 days of treatment, and the existence of neovascularization and inflammation, indicating the recovery and adaptation from the tendon in reaction to the treatment. Overall, this study provides the scientific background and information that helps explain the Ponseti method.
... These results support our study that leucine or other nutrients can increase tenascin synthesis and function. Therefore, the lack of understanding of the relationship between diet and tenascin requires extensive research in this field (64,65). ...
Article
Full-text available
Backgrounds Osteoporosis (OP) is an important risk factor for rotator cuff tears (RCTs). However, the relationship and mechanism between rotator cuff injury and osteoporosis are unclear. Therefore, to investigate association between rotator cuff injury and osteoporosis, and find clinical characteristics, bone mineral density, bone metabolism markers, and nutrient levels in rotator cuff injury patients with or without osteoporosis. Methods One hundred and four cases of patients (RCTs, n=32; RCTs-OP, n=72) who underwent rotator cuff injury and need arthroscopic rotator cuff repair between June 2021 and February 2022, along with the diagnosis of osteoporosis were identified from the dual-energy X-ray bone density screening(DXA). The outcome measure includes clinical characteristics, bone mineral density, bone metabolism markers, vitamins, and amino acids. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation. Results OP with RCTs has a lower level of in 25-vitD, osteocalcin (OCN), serum Ca2+, ornithine, diaminocaproic_acid but the high level of Vitamin_B12, PTH, Vitamin_D3,γ_aminobutyric_acid, Vitamin_C and Vitamin_E than RCTs patients without OP. Predictors contained in the prediction nomogram included lumber T score, femur T score, Niacin_B3, and vitamin D, reflecting the combined effect of vitamins on RCTs-related OP progression. The model has good discriminative ability with a C-index of 0.938(95% CI:-1.83-1.39) and good scaling ability. The high C-index value of 0.95 is still achievable with range validation. Analysis of decision curves showed that non-adherence is clinically useful when intervention decisions are at the 14% probability limit of non-adherence. Conclusion This study supports the hypothesis that lumber T score, femur T score, Niacin_B3, and Vitamin D are valuable prognostic biomarkers on RCTs related OP progression. What is known about the subject It is found that vitamin D are valuable prognostic biomarkers, reflecting the combined effect of vitamins on RCTs related OP progression. What this study adds to existing knowledge These findings also highlight that nutrients condition such as vitamins and amino acids of patients provide a new understanding of the development of RCTs.
Article
In this paper, we show that saturated fatty acids decrease collagen synthesis and make tendons, ligaments, and bone weaker. This means that people who are overweight or eat high saturated fat diets may find that their connective tissues get weaker. This can likely be minimized by proper exercise, but whether exercise can overcome this global change to tendons, ligaments, and bones is still an open question. Also, this could be one reason why it is hard for obese individuals to start, and stick with, an exercise program.
Article
The healing of tendon injury is often hindered by peritendinous adhesion and poor regeneration caused by the accumulation of reactive oxygen species (ROS), development of inflammatory responses, and the deposition of type-III collagen. Herein, an extracellular vesicles (EVs)-cloaked enzymatic nanohybrid (ENEV) was constructed to serve as a multifaceted biocatalyst for ultrasound (US)-augmented tendon matrix reconstruction and immune microenvironment regulation. The ENEV-based biocatalyst exhibits integrated merits for treating tendon injury, including the efficient catalase-mimetic scavenging of ROS in the injured tissue, sustainable release of Zn2+ ions, cellular uptake augmented by US, and immunoregulation induced by EVs. Our study suggests that ENEVs can promote tenocyte proliferation and type-I collagen synthesis at an early stage by protecting tenocytes from ROS attack. The ENEVs also prompted efficient immune regulation, as the polarization of macrophages (Mφ) was reversed from M1φ to M2φ. In a rat Achilles tendon defect model, the ENEVs combined with US treatment significantly promoted functional recovery and matrix reconstruction, restored tendon morphology, suppressed intratendinous scarring, and inhibited peritendinous adhesion. Overall, this study offers an efficient nanomedicine for US-augmented tendon regeneration with improved healing outcomes and provides an alternative strategy to design multifaceted artificial biocatalysts for synergetic tissue regenerative therapies.
Article
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Objectives Lower limb tendinopathy (LLT) is highly prevalent in runners. Treatment can be challenging, and knowledge of risk factors may be valuable to develop preventive or treatment interventions for LLT. The aims of this study were (1) to assess the prevalence of three common LLTs (Achilles tendinopathy (AT), patellar tendinopathy and plantar fasciopathy) in a large cohort of Dutch and Belgian runners and (2) to investigate its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet. Methods A total of 1993 runners were included in the study. They completed two online questionnaires: a general questionnaire on running habits and injuries and a Food Frequency Questionnaire. Runners with and without LLT were compared regarding personal characteristics, running characteristics and nutritional factors. Results The point prevalence for the three LLTs was 6%; 33% of the runners reported LLT in the past and 35% had either a current or past LLT. AT was the most prevalent type of LLT, and prevalence rates for all types of LLT were higher in men than women. Positive associations with LLT were observed for age and running years (men and women), running level and running distance (men). No associations between LLT and nutritional factors were observed. Conclusion One-third of this population of runners had ever experienced an LLT. These tendinopathies were associated with gender, age and running load, but not with nutritional factors.
Article
Full-text available
Tendon is a uniaxial connective tissue component of the musculoskeletal system. Tendon is involved in force transmission between muscle and bone. Tendon injury is very common and debilitating but tendon repair remains a clinical challenge for orthopedic medicine. In vertebrates, tendon is mainly composed of type I collagen fibrils, displaying a parallel organization along the tendon axis. The tendon-specific spatial organization of type I collagen provides the mechanical properties for tendon function. In contrast to other components of the musculoskeletal system, tendon biology is poorly understood. An important goal in tendon biology is to understand the mechanisms involved in the production and assembly of type I collagen fibrils during development, postnatal formation, and healing processes in order to design new therapies for tendon repair. In this review we highlight the current understanding of the molecular and mechanical signals known to be involved in tenogenesis during development, and how development provides insights into tendon healing processes. For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.
Article
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This study aims to investigate the contribution of glucosamine-chondroitin sulphate (GlcN-CS) to the healing of tendons within the bone tunnel. Tendon-to-bone healing was investigated in 28 New Zealand rabbits by re-attaching the extensor digitorum longus tendon into bone tunnel which was created in the proximal tibia. Rabbits were separated into two groups as treatment and control groups. Treatment group (n=14) received 210-250 mg/kg/day glucosamine sulphate and 170-200 mg/kg/day chondroitin sulphate, whereas control group (n=14) received equivalent dose of vehicle. Treatment and control groups were compared at sixth and 12th week after the procedure according to histological and biomechanical analysis. Yamakado scoring system was used to evaluate the histological changes. According to histological analysis, scores were significantly higher at both sixth and 12th week evaluations in the treatment group (p=0.029). Although not statistically significant, the ultimate pullout strength was higher in the treatment group at the 12th week evaluation (35.3 N/mm2 vs. 24.3 N/mm2) (p>0.05). However, stripping occurred at the muscle-tendon junction in the treatment group whereas tendons stripped from the bone tunnels in the control group. While no tendons in the treatment group stripped from the bone tunnels, we observed at sixth and 12th week evaluations that tendons in the control group stripped from the tunnels. Glucosamine-chondroitin sulphate treatment enhances tendon-to-bone healing by increasing hyaline cartilage formation and decreasing formation of capillary vessels.
Article
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Abstract Background: Taurine has anti-inflammatory and antioxidant characteristics. We have introduced taurine into a tendon-healing model to evaluate its effects on tendon healing and adhesion formation. Materials and Methods: 2 groups of 16 rats underwent diversion and repair of the Achilles tendon. One group received a taurine injection (200 mg/ml) at the repair site, while the other group received 1 ml. of saline. Specimens were harvested at 6 weeks and underwent biomechanical and histological evaluation. Results: No tendon ruptured. Average maximum load was significantly greater in the taurine-applied group compared with the control group (p < 0.05). Similarly, average energy uptake was significantly higher in the taurine-applied group compared with the control group (p < 0.05). We observed no significant differences in stiffness in both groups (p > 0.05). After histological assessment, we found that fibroblast proliferation, edema, and inflammation statistically decreased in the treatment group (p < 0.05). Conclusion: These findings could indicate greater tendon strength with less adhesion formation, and taurine may have an effect on adhesion formation.
Article
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Tendon is a crucial component of the musculoskeletal system. Tendons connect muscle to bone and transmit forces to produce motion. Chronic and acute tendon injuries are very common and result in considerable pain and disability. The management of tendon injuries remains a challenge for clinicians. Effective treatments for tendon injuries are lacking because the understanding of tendon biology lags behind that of the other components of the musculoskeletal system. Animal and cellular models have been developed to study tendon-cell differentiation and tendon repair following injury. These studies have highlighted specific growth factors and transcription factors involved in tenogenesis during developmental and repair processes. Mechanical factors also seem to be essential for tendon development, homeostasis and repair. Mechanical signals are transduced via molecular signalling pathways that trigger adaptive responses in the tendon. Understanding the links between the mechanical and biological parameters involved in tendon development, homeostasis and repair is prerequisite for the identification of effective treatments for chronic and acute tendon injuries.
Article
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Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.
Article
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Rotator cuff injuries are a common source of shoulder pathology and result in an important decrease in quality of patient life. Given the frequency of these injuries, as well as the relatively poor result of surgical intervention, it is not surprising that new and innovative strategies like tissue engineering have become more appealing. Tissue-engineering strategies involve the use of cells and/or bioactive factors to promote tendon regeneration via natural processes. The ability of numerous growth factors to affect tendon healing has been extensively analyzed in vitro and in animal models, showing promising results. Platelet-rich plasma (PRP) is a whole blood fraction which contains several growth factors. Controlled clinical studies using different autologous PRP formulations have provided controversial results. However, favourable structural healing rates have been observed for surgical repair of small and medium rotator cuff tears. Cell-based approaches have also been suggested to enhance tendon healing. Bone marrow is a well known source of mesenchymal stem cells (MSCs). Recently, ex vivo human studies have isolated and cultured distinct populations of MSCs from rotator cuff tendons, long head of the biceps tendon, subacromial bursa, and glenohumeral synovia. Stem cells therapies represent a novel frontier in the management of rotator cuff disease that required further basic and clinical research.
Article
Inflammatory processes play essential roles in the pathogenesis of tendinitis and tendinopathy. These events are accompanied by catabolic processes initiated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Pharmacological treatments for tendinitis are restricted to the use of non-steroidal anti-inflammatory drugs. Recent studies in various cell models have demonstrated that curcumin targets the NF-κB signaling pathway. However, its potential for the treatment of tendinitis has not been explored. Herein, we used an in vitro model of human tenocytes to study the mechanism of curcumin action on IL-1β-mediated inflammatory signaling. Curcumin at concentrations of 5-20 μm inhibited IL-1β-induced inflammation and apoptosis in cultures of human tenocytes. The anti-inflammatory effects of curcumin included down-regulation of gene products that mediate matrix degradation (matrix metalloproteinase-1, -9, and -13), prostanoid production (cyclooxygenase-2), apoptosis (Bax and activated caspase-3), and stimulation of cell survival (Bcl-2), all known to be regulated by NF-κB. Furthermore, curcumin suppressed IL-1β-induced NF-κB activation via inhibition of phosphorylation and degradation of inhibitor of κBα, inhibition of inhibitor of κB-kinase activity, and inhibition of nuclear translocation of NF-κB. Furthermore, the effects of IL-1β were abrogated by wortmannin, suggesting a role for the phosphatidylinositol 3-kinase (PI-3K) pathway in IL-1β signaling. Curcumin suppressed IL-1β-induced PI-3K p85/Akt activation and its association with IKK. These results demonstrate, for the first time, a potential role for curcumin in treating tendon inflammation through modulation of NF-κB signaling, which involves PI-3K/Akt and the tendon-specific transcription factor scleraxis in tenocytes.
Article
Understanding the molecular and cellular mechanisms underlying tissue turnover and repair are essential towards addressing pathologies in aging, injury, and disease. Each tissue has distinct means of maintaining homeostasis and healing after injury. For some, resident stem cell populations mediate both of these processes. These stem cells, by definition, are self-renewing and give rise to all the differentiated cells of that tissue. However, not all organs fit with this traditional stem cell model of regeneration, and some do not appear to harbor somatic stem or progenitor cells capable of multilineage in vivo reconstitution. Despite recent progress in tendon progenitor cell research, our current knowledge of the mechanisms regulating tendon cell homeostasis and injury response is limited. Understanding the role of resident tendon cell populations is of great importance for regenerative medicine-based approaches to tendon injuries and disease. The goal of this review is to bring to light our current knowledge regarding tendon progenitor cells and their role in tissue maintenance and repair. We will focus on pressing questions in the field and the new tools, including model systems, available to address them.
Article
Recent research on tendinopathy has focused on its relationship to programmed cell death. Increased autophagy has been observed in ruptured rotator cuff tendon tissues, suggesting a causal relationship. We investigated whether autophagy occurs in human rotator cuff tenofibroblast death induced by oxidative stress and whether antioxidants protect against autophagic cell death. We used H2O2 (0.75 mM) as oxidative stressor, cyanidin (100 µg/ml) as antioxidant, zVAD (20 µM) as apoptosis inhibitor, and 3-MA (10 mM) as autophagy inhibitor. We evaluated cell viability and known autophagic markers: LC3-II expression, GFP-LC3 puncta formation, autolysosomes, and Atg5-12 and Beclin 1 expression. H2O2 exposure increased the rates of cell death, LC3-II expression, GFP-LC3 puncta formation, and autolysosomes. After we induced apoptosis arrest using zVAD, H2O2 exposure still induced cell death, LC3-II expression, and GFP-LC3 puncta formation. H2O2 exposure also increased Atg5-12 and Beclin 1 expressions, indicating autophagic cell death. However, cyanidin treatment reduced H2O2-induced cell death, LC3-II expression, GFP-LC3 puncta formation, and autolysosomes. Cyanidin and 3-MA similarly reduced the cell-death rate, and Atg5-12 and Beclin 1 expression. This study demonstrated that H2O2, an oxidative stressor, induces autophagic cell death in rotator cuff tenofibroblasts, and that cyanidin, a natural antioxidant, inhibits autophagic cell death. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res