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ABSTRACT: The Tokuhashi prognosis score consists of six parameters. The sum of points rated for each parameter can be correlated with the prognosis. This study evaluates the score variations that have been done by different authors and Tokuhashi et al. themselves.
Two hundred and seventeen consecutive patients, surgically treated for vertebral metastases, were studied retrospectively. We calculated the original and modified score of Tokuhashi and evaluated the predictive value for the individual life expectancy.
The original and modified Tokuhashi score assured a significant predictive value. Modified criteria by the authors showed the highest reliability between the predicted and real survival, and the patients could be allocated correctly to the desirable instrumentation.
The original and modified Tokuhashi score showed a significant predictive value. The modified criteria by the authors showed the highest reliability between predicted and real survival.
European Journal of Surgical Oncology 10/2007; 33(7):914-9. · 2.50 Impact Factor
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ABSTRACT: To analyse sports activities of patients with hip or knee osteoarthritis (OA) over lifetime, preoperatively, and 5 years after arthroplasty.
In a longitudinal four centre study, 809 consecutive patients with advanced OA of the hip (420) or the knee (389) joint under the age of 76 years who required total joint replacement were recruited. A completed questionnaire about sports activities at 5 year follow up was received from 636 (79%) of the 809 patients.
Although most patients with hip (97%) and knee (94%) OA had performed sports activities during their life, only 36% (hip patients) and 42% (knee patients) had maintained sports activities at the time of surgery. Five years postoperatively, the proportion of patients performing sports activities increased to 52% among patients with hip OA, but further declined to 34% among those with knee OA. Accordingly, the proportion of patients with hip OA performing sports activities for more than 2 hours a week increased from 8 to 14%, whereas this proportion decreased from 12 to 5% among patients with knee OA. Pain in the replaced joint was reported by 9% of patients with hip and by >16% with knee OA.
Differences in pain 5 years after joint replacement may explain some of the difference of sports activities between patients with hip and knee OA. Reasons for reduction of sports activities may include the increasing age of the patients, their worries about an "artificial joint", and the advice of their surgeon to be cautious.
Annals of the Rheumatic Diseases 12/2005; 64(12):1715-20. · 8.73 Impact Factor
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ABSTRACT: Diabetic muscle infarction (DMI) is a largely unfamiliar disease. It affects mainly patients around 40 years of age with long-standing diabetes and concomitant end-organ complications. The symptoms represent a classic pattern of a musculoskeletal disease with muscle pain without trauma, swelling, and functional impairment. Although its short-term prognosis is good, with improvement of the symptoms over weeks or months under analgesia and rest, a high recurrence rate of up to 60% can be observed. Additionaly, the long-term survival of patients after DMI is reduced mostly due to major vascular complications. Since many diabetic patients are in orthopedic care for musculoskeletal disorders, the orthopedic surgeon should be aware of this disease to avoid unnecessary invasive diagnostic procedures and initiate suitable therapy. Furthermore, a better knowledge of the disease could lead to definite conclusions regarding its real incidence and aid in establishing new therapeutic measures for prophylaxis and better long-term survival.
Der Orthopäde 04/2005; 34(3):210, 212-7. · 0.51 Impact Factor
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ABSTRACT: The aim of this study was to improve the management of cervical tumor osteolysis. A new modular rod-screw implant system for the posterior instrumentation of the occipito-cervical, cervical and cervico-thoracic spine (neon occipito cervical system, Ulrich, Germany) is available since 2000. K-wire guided pedicle screws are used, CT-guided instrumentation is possible. Previous studies have demonstrated increased biomechanical stability compared to established posterior cervical systems.
The cervical and cervico-thoracic spine of 8 patients (6 males, 2 females, mean age 62 years, range 48-77 years) with osteolysis due to plasmocytoma (n=2), bronchial (n=2), mammary (n=2), esophageal (n=1) and pancreatic (n=1) carcinoma were instrumentated since June 2001.
A stable fixation without loosening or failure of the fixation system was achieved in all cases. No impairment of the neurogical status was observed.
Posterior instrumentation of the cervical spine including the occipito-cervical and the cervico-thoracic region with a new modular angle-stable rod-screw implant system offers good stabilization and allows simultaneous decompression. Since tumor masses are predominantly located in the anterior portion of the spine blood loss can be reduced.
European Spine Journal 06/2004; 13(3):222-8. · 1.97 Impact Factor
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ABSTRACT: Our aim was to investigate the maintenance of the transfection status of non-viral transfected chondrocytes in an alginate culture system.
Chondrocytes harvested from rabbit knees were isolated by sequential digestion and cultivated in monolayer culture. At 60-70% cell density, chondrocytes were transfected with different transfection systems (FuGENE6, CaCl2, Lipofectin). A lac Z expression vector (pcDNA 3.1/Myc-His+ lacZ) was used as a reporter system. In order to improve transfection rates, hyaluronidase (4 U/ml) was used prior and during the transfection procedure. Thereafter, transfected cells were either kept in monolayer culture or embedded in alginate beads and kept in culture for up to the next 30 weeks.
Transfection efficiency was maximal using FuGENE6TM/DNA at a ratio of 3:2 and hyaluronidase (4 U/ml). Transfection efficiency reached up to 40.8% (+/- 3.2%) after 36 h. In alginate beads lac Z positive cells declined to 8.5% +/- 3.3% after 4 weeks and to 4.6% +/- 3.2% after 12 weeks of culturing. After 30 weeks 3% of chondrocytes still expressed lac Z. In contrast, during culturing in monolayer, no lac Z expression was detectable after 4 weeks. Differentiation status of the chondrocytes was confirmed by histology and immunohistochemistry methods.
After successful gene transfer to rabbit chondrocytes the alginate system made it possible to culture lipofected chondrocytes phenotypically stable. Genetically engineered chondrocytes express the lac Z reporter gene over a period of at least 30 weeks. This transfection and culture system provides a promising tool to further investigate the over-expression of growth factors and enzyme inhibitors.
Osteoarthritis and Cartilage 04/2002; 10(3):212-7. · 3.90 Impact Factor
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ABSTRACT: In order to characterize the consequences for the process of endochondral ossification we performed an immunohistochemical study and compared the expression of collagen type I, II and X as markers of cartilage differentiation and Ki-67 as a marker of cell proliferation in solitary (7-26 years, n=9) and multiple (11-42 years, n=6) osteochondromas with their expression in human fetal and postnatal growth plates. In fetal and young postnatal controls, we found a thin superficial layer of articular cartilage that stained positive for collagen type I while collagen II was expressed in the rest of the cartilage and collagen type X was restricted to the hypertrophic zone. Osteochondromas from children showed lobular collagen type II-positive areas surrounded by collagen type I. In adults, the separation of collagen type I- and type II-positive areas was more blurred, or the cartilaginous cap was missing. Collagen type X was detected in a pericellular distribution pattern within hypertrophic zones but also deeper between bone trabecula. The proliferative activity of osteochondromas from children younger than 14 years of age was comparable to postnatal growth plates, whereas in cartilage from individuals older than 14 years of age, we could not detect significant proliferative activity.
European journal of histochemistry: EJH 02/2002; 46(3):249-58. · 1.69 Impact Factor
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ABSTRACT: Culture of articular chondrocytes in alginate beads offers several advantages over culture in monolayer; cells retain their phenotype for 8 months or longer. Earlier studies of chondrocytes cultured in alginate concentrated on collagen and proteoglycan synthesis. However, gene expression by in situ hybridization (ISH) has not been investigated. The purposes of the present study on human chondrocytes were (a) to modify the ISH procedure for the alginate beads to examine the mRNA expression of alpha1 (II) procollagen, aggrecan, and two matrix metalloproteinases (MMP-3 and MMP-8) thought to be involved in cartilage matrix degradation, and (b) to compare expression in cultured chondrocytes with that in chondrocytes of intact human cartilage. The modifications made for ISH include the presence of CaCl2 and BaCl2 in the fixation and washing steps and exclusion of cetyl pyridinium chloride. By ISH we show that aggrecan, MMP-3, and MMP-8 are continuously expressed during 8 months of culture. The alpha1 (II) procollagen gene is expressed only during the first 2 months of culture and after 3 months its expression is undetectable, which is consistent with its absence in adult articular cartilage. By Western blotting, Type II collagen protein had been synthesized and deposited in both the cell-associated and further-removed matrix compartments at 7 and 14 days of culture. These data indicate that chondrocytes cultured in alginate beads could be preserved for immunohistochemistry and ISH and that culture of human chondrocytes in alginate beads may serve as a good model for studying cartilage-specific phenotype as well as factors that influence cartilage matrix turnover.
Journal of Histochemistry and Cytochemistry 11/2001; 49(10):1211-20. · 2.72 Impact Factor
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ABSTRACT: Clinical experience shows that symptoms and pathological changes of primary osteoarthritis (OA) are more frequent and severer in the knee than in the ankle joint. The different anatomy of both weight-bearing joints implies that biomechanical differences may contribute to their varying susceptibility to OA. This study aims at elucidating other non-biomechanical factors to explain these fundamental differences in secondary OA prevalence. Human cartilage of matched ankle and knee joints from organ donors was dissected in full-thickness slices or in layers. The DNA content for estimation of cell number was analyzed fluorometrically. Chondrocytes were cultured in organ culture or after isolation in alginate. Proteoglycan synthesis was determined by 35S incorporation, and collagen synthesis by 3H-proline incorporation. This study demonstrates that in both joints, the cell density sharply declines between newborn and young infant ages. In addition, cartilage from the ankle joint is significantly more cellular than cartilage from the knee joint. In general, ankle chondrocytes synthesize more proteoglycans (PGs) and collagens than knee chondrocytes, and deep zone chondrocytes more than superficial zone chondrocytes. The biochemical properties of chondrocytes of the ankle and knee joints differ significantly and might play an important role in the pathogenesis of OA.
Archives of Orthopaedic and Trauma Surgery 07/2001; 121(6):301-6. · 1.37 Impact Factor
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ABSTRACT: To analyze cartilage gene expression of patients with osteoarthritis (OA) in correlation with radiographic and histological findings.
Twenty-one patients with OA of the knee admitted for total knee replacement were analyzed clinically and radiographically by the Kellgren and Lawrence system. During surgery, cartilage samples from the medial and lateral condyles and tibial plateaus were harvested separately. Specimens were analyzed histologically (Mankin score) and total RNA was extracted directly from cartilage tissue. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR.
Histology of medial and lateral knee compartments corresponded to radiographic changes (Spearman correlation coefficient: r = 0.7 (p < 0.01)). There was a positive correlation between MMP-3 and AGG gene expression (r = 0.4; p < 0.01). We found considerable variation of expression levels of MMP-3 and AGG and no correlation of gene expression with histological or radiographic scoring.
The positive correlation between AGG and MMP-3 suggests a common regulation of anabolic and catabolic metabolism. There was no simple dependency between gene expression and histological and radiological findings in cartilage.
Pathobiology 01/2001; 69(6):333-8. · 1.18 Impact Factor
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ABSTRACT: The treatment of lumbar cerebrospinal fluid fistula in the presence of an intrathecal catheter is known to be difficult. Open revision surgery is recommended in the literature, although the rate of recurrence is high. The epidural blood patch technique is well established as a successful treatment for post-dural-puncture headaches. Recent work about the distribution of the injected blood and theoretical considerations about the mechanism of action make this method suitable for the occlusion of spinal leakage even in the presence of an intrathecal catheter. In this note technical details are given for a successful therapy of lumbar cerebrospinal fluid fistula including the right positioning of the opening of the needle (cerebrospinal fluid can be expected intrathecally and epidurally) by injection of contrast medium first for myelography then for epidurography. In this procedure the (epidural) distribution of autologous blood can be indirectly controlled by compression of the dural sac. The method is easy to perform, and the possible risks are small.
Spinal Cord 10/1999; 37(9):648-52. · 1.80 Impact Factor
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ABSTRACT: Recombinant human osteogenic protein 1 (OP-1) is an effective stimulator of human cartilage 35S-proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP-1 can help overcome interleukin-1beta (IL-1beta)-induced suppression of 35S-proteoglycan synthesis.
Human articular chondrocytes in alginate beads were maintained for 3 days in the absence (control) or presence of IL-1beta at 0.1-100 pg/ml with or without OP-1 at 50 ng/ml, in medium containing 10% fetal bovine serum (FBS). Incorporation of 35S-sulfate into proteoglycans was quantified during the last 4 hours of culture and reported as counts per minute per microg DNA. Release of interleukin-1 receptor antagonist (IL-1Ra) and prostaglandin E2 into the medium was monitored by immunoassay.
IL-1beta at 10 pg/ml caused a 60% decrease in 35S-proteoglycan synthesis. This could be blocked by including 500 ng/ml IL-1Ra in the medium. The presence of 50 ng/ml OP-1 in the IL-1beta-containing medium was effective in restoring 35S-proteoglycan synthesis to the level of that found in cultures not treated with IL-1beta. The restorative effects of OP-1 and IL-1Ra were cumulative. The rate of release of prostaglandin E2 and IL-1Ra into the medium was not affected by the presence of OP-1.
Treatment of human articular chondrocytes with OP-1 cultured in the presence of FBS is effective in overcoming the down-regulation of proteoglycan synthesis induced by low doses of IL-1beta.
Arthritis & Rheumatism 01/1998; 40(12):2157-61. · 7.87 Impact Factor
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Rontgenpraxis 07/1997; 50(6):142-9.
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ABSTRACT: To detect the message for membrane type 1 (MT1) matrix metalloproteinase (MMP) in articular cartilage and chondrosarcoma cells, to study its expression in osteoarthritis (OA), and to determine whether interleukin-1beta (IL-1beta) influences its expression.
Reverse transcription-polymerase chain reaction methods were used to detect message. Cloning and sequencing were applied to confirm the sequence. Northern blotting was used to quantify the message for MT1-MMP and to compare its expression in OA cartilage with or without IL-1beta treatment. In situ hybridization was utilized to show MT1-MMP transcripts in cartilage and to study the influence of IL-1beta.
The results show that MT1-MMP messenger RNA (mRNA) is expressed in chondrosarcoma cells and OA chondrocytes. Results of the in situ hybridization confirmed the expression in OA cartilage as well as in normal cartilage. The level of mRNA was not modulated following IL-1beta stimulation.
This study shows that MT1-MMP is expressed by chondrocytes. The similarities in mRNA levels in OA and normal chondrocytes suggest that regulation of MT1-MMP mRNA may not be a primary factor in OA.
Arthritis & Rheumatism 05/1997; 40(4):704-9. · 7.87 Impact Factor
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ABSTRACT: Ankle and knee joints differ in their susceptibility to osteoarthritis (OA). This article reviews literature on differences between these joints. A Medline search and search of bibliographies of review articles was conducted. Knee cartilage degeneration leads to the development of OA with clinical symptoms, whereas the ankle cartilage develops fissures that do not appear to progress to later stages of OA. Epidemiological studies support these findings. Factors that might explain this phenomena include differences in joint motion, cartilage thickness, congruency, mechanical forces, and even evolutionary changes. Data suggest that chondrocytes from the two joints may respond differently to stimuli. Comparisons of cartilage from the knee and ankle joint of the same donor may provide a better understanding of the biochemical and molecular processes that induce the pathogenesis of OA and may provide new approaches to early detection and treatment.
Seminars in Arthritis and Rheumatism 03/1997; 26(4):667-74. · 4.97 Impact Factor
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ABSTRACT: Information on the prevalence and extent of degenerative morphological changes (DMC) in the joints of the lower extremity, including foot joints is sparse. In the present study, the first and fifth metatarsalphalangeal (MTP), transverse tarsal, subtalar, talocrural, knee and hip joints of 50 cadavers were examined grossly and graded on a five-point scale for signs of DMC. Selected samples were examined histologically. Our results confirm clinical findings that severe DMC in foot joints are uncommon except in the first MTP joint where the plantar aspect is most affected. The knee joint displayed the most numerous and severe signs of DMC followed by the first MTP joint. The hip, talocrural, subtalar and transverse tarsal joints displayed comparatively moderate levels of DMC while the fifth MTP was rarely affected. The only joint to display significantly greater levels of DMC on the distal side of the joint as compared with the proximal side, when a difference was present, was the hip. There were significantly greater levels of DMC on the medial aspect of two or more joints within an extremity than on the lateral aspect. Radiographs often showed few or no signs of DMC even when erosion down to subchondral bone was observed upon gross examination.
Osteoarthritis and Cartilage 02/1997; 5(1):23-37. · 3.90 Impact Factor
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ABSTRACT: Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 microM Fn-f temporarily suppresses PG synthesis and enhances MMP release. The higher concentrations cause an initially rapid PG depletion during the first week of culture, followed by much slower PG loss and gradually increasing rates of PG synthesis. To test for the involvement of mediators, human articular cartilage was cultured with Fn-f, and conditioned media were assayed for selected cytokines and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth factor-I and transforming growth factor beta1, from cultured cartilage was enhanced by 50-100% during the entire 28-day culture period and this was associated with both supernormal rates of PG synthesis and PG content. However, the higher concentrations of Fn-f additionally enhanced release, by at least 10-fold, of the cytokines, tumour necrosis factor alpha, interleukin-1alpha, interleukin-1beta and interleukin-6 while causing depletion of cartilage PG. Release of tumour necrosis factor alpha, interleukin 1beta and interleukin 1alpha peaked at days 2, 3 and 9 during or slightly after the period of maximal PG depletion and decreased to control levels by days 7, 7 and 21 respectively, whereas release of interleukin 6 was enhanced throughout the culture period. Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3 release and suppression of PG synthesis. The temporal aspects of this interplay between catabolic and anabolic factors are consistent with the kinetics of Fn-f-mediated cartilage damage and attempted repair and may be relevant to cartilage damage and repair in vivo.
Biochemical Journal 02/1997; 321 ( Pt 3):751-7. · 4.90 Impact Factor
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ABSTRACT: To study the effects of recombinant human osteogenic protein-1 (rHuOP-1; bone morphogenetic protein-7) on proteoglycan and collagen synthesis by human articular chondrocytes.
Articular chondrocytes from fetal, adolescent, and adult human donors were cultured in alginate beads for 4 days in a mixture of Ham's F-12, Dulbecco's modified Eagle's medium, 10% fetal bovine serum (FBS), then for an additional 3-10 days in the presence and absence of rHuOP-1, with and without FBS. Chondrocyte synthetic activity was measured as the amount of incorporation of 35S-sulfate into proteoglycans and 3H-proline into hydroxyproline. Sieve chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were performed to identify specific proteoglycans and collagens.
Recombinant human OP-1 markedly stimulated the synthesis of proteoglycans (mostly aggrecan) and collagens (predominantly type II) by all chondrocyte preparations. This did not require the presence of FBS and was associated with continued expression of the chondrocyte phenotype.
Recombinant human OP-1 is a more potent stimulator of the synthesis of cartilage-specific molecules by human articular chondrocytes than are other factors tested for comparison, including TGF beta 1 and activin A.
Arthritis & Rheumatism 12/1996; 39(11):1896-904. · 7.87 Impact Factor
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ABSTRACT: Ultrahigh-molecular dextran (500,000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline?
Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70,000 Da (DEX-70), 160,000 Da (DEX-160), 300,000 Da (DEX-300) or 500,000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg.
Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p < 0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70.
Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.
Intensive Care Medicine 11/1996; 22(11):1207-13. · 5.40 Impact Factor
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ABSTRACT: This study confirms that normal human articular chondrocytes express neutrophil collagenase or matrix metalloproteinase-8 (MMP-8), a gene product previously thought to be expressed exclusively by neutrophil leukocytes. Both MMP-8 protein and mRNA were present in articular cartilages collected from normal human donors. Cartilage extracts were assayed by immunoblotting and by analysis of enzymatic activity on gelatin-substrate gels. Latent MMP-8 extracted from cartilage has a molecular mass of 55 kDa; active MMP-8 was identified at 46 and 42 kDa. In the absence of a reducing agent, MMP-8 migrated in a high molecular mass complex above 200 kDa. Northern blotting results demonstrated the expression of MMP-8 in chondrocytes, which could be up-regulated by stimulation with interleukin-1 beta. In addition, reverse transcription-polymerase chain reaction using nested primers and in situ hybridization revealed the presence of MMP-8 mRNA in chondrocytes. The presence of both MMP-8 protein and message in cartilage supports the concept that neutrophil collagenase could be the enzyme described as "aggrecanase".
Journal of Biological Chemistry 06/1996; 271(18):11023-6. · 4.77 Impact Factor
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ABSTRACT: The loss of aggrecan from articular cartilage may lead to the development of osteoarthritis (OA). Degradation products of human aggrecan, generated in vivo by enzymatic cleavages, have been identified in synovial fluid of patients with rheumatoid arthritis and OA. One matrix metalloproteinase (MMP), stromelysin (MMP-3), and an unidentified proteinase called "aggrecanase" are believed to generate these products in pathologic conditions. Thus far, only one proteinase, neutrophil collagenase (MMP-8), has been shown in vitro to be capable of cleavage of the aggrecan molecule at the "aggrecanase" site. In this study, we compare the presence and distribution of MMP-3 and MMP-8 in cartilages from two different joints of normal human donors. We determined whether mRNA for MMP-8 is expressed in normal human articular cartilage from different joints. In addition, we compared differences in MMP-8 and MMP-3 gene expression between human ankle and knee cartilage after in vitro stimulation by interleukin (IL)-1 beta. These two joints were chosen because the incidence of symptomatic and radiographic OA varies between the different joints. The knee is the most frequently involved joint, whereas the ankle (talocrural) joint is relatively rarely affected. Message for MMP-8 was detected in untreated cartilage from normal knee joints, but not in untreated cartilage of normal ankle joints. Message for MMP-3 was detectable in most of the knee and ankle cartilages. Messenger RNA expression for both MMPs could be up-regulated by IL-1 beta. The highest doses of IL-1 beta appeared to be most effective in stimulation of mRNA for MMP-3, whereas MMP-8 expression was more sensitive to lower doses of IL-1 beta. The fact that ankle cartilage with a low incidence of OA does not express MMP-8, whereas knee cartilage with a high incidence of OA does not express MMP-8, whereas knee cartilage with a high incidence of OA does constitutively express MMP-8, suggests that MMP-8 might be one of the key enzymes in the pathogenesis of osteoarthritis. This is further supported by our finding that the earliest signs of cartilage degradation were very similar to those found in IL-1 beta-treated explants.
Laboratory Investigation 02/1996; 74(1):232-40. · 3.64 Impact Factor
