[Show abstract][Hide abstract] ABSTRACT: In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques.
Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed.
The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade.
T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.
[Show abstract][Hide abstract] ABSTRACT: We have previously studied the effects of chondrocyte sheets on the repair and regeneration of articular cartilage by using temperature-responsive culture inserts. On the basis of this work, we succeeded in rapid fabrication of chondrocyte sheets with the use of a coculture method in which inserts were placed between synoviocytes and chondrocytes. Treatment of cartilage defects using layered chondrocyte sheets promotes repair and regeneration; this method is compatible with in vivo osteoarthritis (OA) models that reproduce partial-thickness defects. In human stem cell clinical research guidelines, the Ministry of Health, Labour and Welfare (MHLW) approved several applications related to this technology. Indeed, its translation to a clinical setting is already yielding favorable results. Here, we evaluated the risk of tumorigenesis associated with this treatment and characterized the dynamics of biological processes associated with the post-transplantation cell sheets in vivo. Furthermore, we also confirmed the safety of the procedure by using array comparative genomic hybridization (array CGH) and G-band staining to screen for deleterious genetic aberrations during prolonged subculture of cells. The safety of chondrocytes that were cultured for longer than normal was confirmed by the array CGH and G-band staining results. Additionally, tumorigenicity testing confirmed that culture chondrocyte sheets are not tumorigenic. Furthermore, from the evaluation of bioluminescence imaging following implantation of the cell sheets, it was confirmed that the transplanted chondrocytes and synoviocytes remained in the knee joint and did not transfer elsewhere over time. We believe that the technique used in this study is a highly useful method for evaluating the safety of not only chondrocytes, but extensive subculturing in general.
Tissue Engineering Part C Methods 11/2015; DOI:10.1089/ten.TEC.2015.0254 · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Prevention and early detection of venous thromboembolism (VTE) is important after arthroplasty of the lower limb. The purpose of this study was to investigate the associations between VTE and hemostatic markers after minimally invasive total knee arthroplasty (MIS-TKA).
We performed a retrospective study of 50 patients (55 knees) who underwent primary unilateral MIS-TKA with periodic determination of D-dimer and soluble fibrin monomer complex (SFMC) concentrations and with ultrasonography. The development of symptomatic and asymptomatic VTE, location of deep venous thrombosis (DVT; proximal or distal), changes in SFMC and D-dimer concentrations, and correlations between hemostatic markers and VTE onset were evaluated.
Twenty-six patients (47 %) had an asymptomatic distal DVT, but none had proximal DVT, pulmonary embolism, or symptomatic DVT. DVT was detected at postoperative day 1 (POD1) in 16 patients, POD3 in six, and POD5 in three (excluding detections of the same DVT in the same position on different days). DVT onset correlated significantly with SFMC concentration on POD1 and with D-dimer concentration on POD3. The D-dimer concentration did not differ significantly between patients who developed DVT (DVT+) and those who did not (DVT-) at each postoperative time. SFMC concentration differed between DVT+ and DVT- patients only on POD1. Analysis of each hemostatic marker classified as either within or outside the normal concentration range showed no significant correlations between D-dimer concentration and DVT onset at each period. There were significant correlations between SFMC concentrations and DVT onset on POD1 and POD3. There were also significant correlations between D-dimer positive (+) findings and/or SFMC+ findings and DVT onset on POD1 and POD3. D-dimer+ and/or SFMC+ findings had better specificity on POD1 and a positive predictive value on POD1 and POD3 compared with SFMC+ alone.
SFMC concentration is an effective hemostatic marker for early detection of DVT. D-dimer concentration alone has limited value as a hemostatic marker for early detection of DVT. Measurement of both D-dimer and SFMC concentrations might be a more sensitive diagnostic tool than measuring SFMC concentration alone.
Journal of Orthopaedic Surgery and Research 11/2015; 10(1):172. DOI:10.1186/s13018-015-0315-4 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor alpha (TNF-α) is important in the process of intervertebral disc (IVD) degeneration because of its ability to regulate other inflammatory mediators in autocrine and paracrine fashions. The mechanism responsible for the cell type-specific regulation of TNF-αis not well known. CCAAT/enhancer binding protein β (C/EBPβ) is one of the transcriptional factors that is implicated in TNF-αexpression. However, it is not known whether cross talk occurs between C/EBPβand the TNF-αpathway in IVD cells. The expression and effect of the C/EBPβmRNA and protein in rat IVD cells was assessed using real-time reverse transcription polymerase chain reaction, immunohistochemical, and immunofluorescence analyses. We present data that show that the C/EBPβmRNA and protein were expressed in rat and human IVDs in vivo. We also found that the expression of TNF-αis regulated by the transcription factor C/EBPβ in rat NP cells. The TNF-αpromoter was suppressed completely in the presence of the ERK inhibitor PD98059 and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not in the presence of the JNK inhibitor SP600125. In addition, gain and loss of function analyses showed that the expression of TNF-αwas regulated by C/EBPβ through the MAPK pathways. These findings showed that C/EBPβacts as a potent pro-inflammatory mediator by inducing the TNF-α gene at the transcription and protein levels via the ERK1/2 and p38 pathways in rat NP cells. Our findings may open a new avenue toward the understanding of the cellular and molecular mechanisms of IVD cells. This article is protected by copyright. All rights reserved.
Journal of Orthopaedic Research 10/2015; DOI:10.1002/jor.23085 · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present a case of carpal tunnel syndrome involving wrist trigger caused by a hypertrophied lumbrical muscle with flexor synovitis. The case was a 40-year-old male heavy manual worker complaining of numbness and pain in the median nerve area. On active flexion of the fingers, snapping was observed at the carpal area, and forceful full grip was impossible. Tinel’s sign was positive and an electromyographic study revealed conduction disturbance of the median nerve at the carpal tunnel. Magnetic resonance imaging revealed edematous lumbrical muscle with synovial proliferation around the flexor tendons. Open carpal tunnel release was performed under local anesthesia. Synovial proliferation of the flexor tendons was found and when flexing the index and middle fingers, the lumbrical muscle was drawn into the carpal tunnel with a triggering phenomenon. After releasing the carpal tunnel, the triggering phenomenon and painful numbness improved.
[Show abstract][Hide abstract] ABSTRACT: The cyclooxygenase 2 (COX-2) product, prostaglandin E2 (PGE2 ), acts through a family of G protein- coupled receptors designated E-prostanoid (EP) receptors that mediate intracellular signaling by multiple pathways. However, it is not known whether crosstalk between tumor necrosis factor-α(TNF-α)- PGE2 -mediated signaling and Wnt signaling plays a role in the regulation of intervertebral disc (IVD) cells. In this study, we investigated the relationship between TNF-α-PGE2 signaling and Wnt signaling in IVD cells. TNF-αincreased the expression of COX-2 in IVD cells. The EP receptors EP1, EP3, and EP4 were expressed in IVD cells, and TNF-αsignificantly increased PGE2 production. Stimulation with TNF-αalso upregulated EP3 and EP4 mRNA and protein expression in IVD cells. The inductive effect of the EP3 and EP4 receptors on Topflash promoter activity was confirmed through gain- and loss-of-function studies using selective EP agonists and antagonists. PGE2 treatment activated Wnt-β-catenin signaling through activation of EP3. We conclude that TNF-α-induced COX-2 and PGE2 stimulate Wnt signaling and activate Wnt target genes. Suppression of the EP3 receptor via TNF-α-PGE2 signaling seems to suppress IVD degeneration by controlling the activation of Wnt signaling. These findings may help identify the underlying mechanism and role of Wnt signaling in IVD degeneration. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Orthopaedic Research 06/2015; 33(12). DOI:10.1002/jor.22959 · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Skeletal muscle makes up 40-50% of body mass, and is thus considered to be a good adult stem cell source for autologous therapy. Although, several stem/progenitor cells have been fractionated from mouse skeletal muscle showing a high potential for therapeutic use, it is unclear whether this is the case in human. Differentiation and therapeutic potential of human skeletal muscle-derived cells (Sk-Cs) was examined. Samples (5-10 g) were obtained from the abdominal and leg muscles of 36 patients (age, 17-79 years) undergoing prostate cancer treatment or leg amputation surgery. All patients gave informed consent. Sk-Cs were isolated using conditioned collagenase solution, and were then sorted as CD34-/CD45-/CD29+ (Sk-DN/29+) and CD34+/CD45- (Sk-34) cells, in a similar manner as for the previous mouse Sk-Cs. Both cell fractions were appropriately expanded using conditioned culture medium for about 2 weeks. Differentiation potentials were then examined during cell culture and in vivo transplantation into the severely damaged muscles of athymic nude mice and rats. Interestingly, these two cell fractions could be divided into highly myogenic (Sk-DN/29+) and multipotent stem cell (Sk-34) fractions, in contrast to mouse Sk-Cs, which showed comparable capacities in both cells. At 6 weeks after the separate transplantation of both cell fractions, the former showed an active contribution to muscle fiber regeneration, but the latter showed vigorous engraftment to the interstitium associated with differentiation into Schwann cells, perineurial/endoneurial cells, and vascular endothelial cells and pericytes, which corresponded to previous observations with mouse SK-Cs. Importantly, mixed cultures of both cells resulted the reduction of tissue reconstitution capacities in vivo, whereas co-transplantation after separate expansion showed favorable results. Therefore, human Sk-Cs are potentially applicable to therapeutic autografts and show multiple differentiation potential in vivo.
Frontiers in Physiology 06/2015; 6:165. DOI:10.3389/fphys.2015.00165 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report of a pathological fracture of the middle phalanx of the little finger due to periosteal chondroma. The periosteal chondroma occupied an extensive area of the middle phalanx extending to the proximal interphalangeal joint, and the fracture involved the distal interphalangeal articular surface. The fracture was internally fixed using a strut bone grafting after resection of the chondroma. One year and four months after the operation, remodeling of the phalanx had completed without recurrence and functional loss.
Hand Surgery 06/2015; 20(2):322-4. DOI:10.1142/s0218810415720156
[Show abstract][Hide abstract] ABSTRACT: We previously reported that low-intensity pulsed ultrasound (LIPUS) treatment after intramedullary nailing of femoral shaft fractures effectively promotes early bone healing. In this study, we examined whether porosis occurs on the side treated with LIPUS by prospectively comparing the treatment and non-treatment groups.
After we performed intramedullary nailing in 17 patients (12 men and 5 women) with AO type A femoral shaft fracture, the patients were divided into the LIPUS treatment group (n = 8) and non-treatment group (n = 9) for examination. Using front and side postoperative plain radiography, we examined whether porosis occurred significantly on the treated side by evaluating the appearance order of anterior, posterior, lateral, and medial calluses and days required for bridging callus formation.
In the treatment group, the mean appearance order of the anterior callus was 1.5 months, earlier than those of the posterior and medial calluses (3.5 and 2.9, respectively), whereas the order of the lateral callus was 2.2, earlier than that of posterior callus (P < 0.05). Meanwhile, no significant differences were observed in the appearance orders of the calluses in the non-treatment group. When the 2 groups were compared, only the appearance order of the anterior callus was earlier in the treatment group (1.5 vs. 2.7; P = 0.02). The days required for bridging callus formation was shorter in the anterior side (44 days in average) than in the posterior side (93 days in average) only in the treatment group (P = 0.02). When the 2 groups were compared, the bridging callus of the only anterior side was formed earlier (P = 0.03) in the treatment group (44 vs. 78 days).
Induction of porosis occurred from the anterior and lateral sides, which were treated with LIPUS after intramedullary nailing of the femoral shaft fractures.
[Show abstract][Hide abstract] ABSTRACT: Degeneration of the lumbar intervertebral discs is irreversible, with no treatment currently available. Building upon experimental studies that demonstrated the importance of the nucleus pulposus (NP) in preserving disc structure, we demonstrated that reinsertion of NP cells slowed further disc degeneration and that direct cell-to-cell contact co-culture with mesenchymal stromal cells (MSCs) significantly upregulated the viability of NP cells in basic and pre-clinical studies in vitro and in vivo using animal models and human cells. Here, we report a 3-year result of a prospective clinical study, aimed to assess the safety and efficacy of activated NP cell transplantation in the degenerate lumbar intervertebral disc. Candidates were 9 patients aged 20-29 years who had Pfirrmann's grade III disc degeneration at the level adjacent to the level scheduled for posterior lumbar intervertebral fusion. Viable NP cells from the fused disc were co-cultured in direct contact with autologous bone marrow-derived MSCs. One million activated NP cells were transplanted into the degenerated disc adjacent to the fused level at 7 d after the first fusion surgery. No adverse effects were observed during the 3-year follow-up period. Magnetic resonance imaging did not show any detrimental effects to the transplanted discs and revealed a mild improvement in 1 case. No cases reported any low back pain. Our clinical study confirmed the safety of activated NP cell transplantation, and the findings suggest the minimal efficacy of this treatment to slow the further degeneration of human intervertebral discs.
[Show abstract][Hide abstract] ABSTRACT: Purpose To examine the impact that neuropathic or nociceptive pain has on the quality of life (QOL) in patients with low back pain (LBP) using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and the Japanese version of the PainDETECT Questionnaire (PDQ-J). Methods Between June 2012 and December 2013, 650 new patients were treated at our institution for LBP. All patients between the ages of 20 and 79 were asked to complete a set of questionnaires including the PDQ-J, a pain visual analog scale (VAS), the JOABPEQ, and the Short Form 36 (SF-36). Based on the PDQ-J scores, participants were classified into three groups: a neuropathic pain group, a nociceptive pain group, and an intermediate mixed pain group. Among them, patients with clear neuropathic and nociceptive LBP were selected. To investigate the differences between neuropathic and nociceptive LBP, diagnosis of spinal disorder, prevalence, age, gender, duration of symptoms, VAS scores, and self-reported general health (SF-36 and JOABPEQ) were compared between the neuropathic and nociceptive pain groups. Results Of 650 patients with LBP, 331 completed the questionnaires and were enrolled in the study. There were 193 men (58.3 %) and 138 women (41.7 %) with a mean age of 54.5 years (range 20–79 years). From the PDQ-J survey, 49 patients (15 %) were classified as having neuropathic pain, and 190 (58 %) were categorized as having nociceptive pain. Patients in the neuropathic pain group had significantly higher VAS scores and lower SF-36 and JOABPEQ scores compared to the nociceptive pain group. Conclusion We examined the impact of nociceptive or neuropathic LBP on QOL. A comparison of JOABPEQ scores between LBP patients assessed by PDQ-J as having neuropathic pain or nociceptive pain suggests that neuropathic pain affects the social and psychological well-being of LBP patients.
European Spine Journal 12/2014; 24(3). DOI:10.1007/s00586-014-3723-y · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionAngiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection.Methods
First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group).ResultsHistologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group.Conclusions
Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.
[Show abstract][Hide abstract] ABSTRACT: In anatomic anterior cruciate ligament (ACL) reconstruction, several pitfalls in creating the femoral bone tunnels at the correct position are of great concern. Our new method, the tibia rotational (TR) technique, may contribute to resolving these. The purpose of this study is to describe further details about the TR technique in anatomic double-bundle ACL reconstruction. Both anteromedial and posterolateral femoral bone tunnels were drilled through a posterolateral tibial bone tunnel using tibial rotation without deep knee flexion. When it is difficult to reach the mark with the rigid guide pin, the narrow curved TR technique guide and the flexible drill system allow drilling femoral bone tunnels in the correct position. The TR technique offers the technical ease required for widespread acceptance while prioritizing the fundamental goals of an anatomic double-bundle ACL reconstruction.
[Show abstract][Hide abstract] ABSTRACT: Background:
Immobilization of the wrist joint with a splint is an established approach for ulnar-sided pain due to ulnocarpal abutment syndrome. However, patients have a tendency to stop wearing the splints because of its inconvenience and there have been no reports based on splint therapy.
We investigated the usefulness of a newly designed custom-made aluminum splint for ulnar-sided wrist pain.Study design: This was a cohort study of the aluminum splint therapy for the patients who had been primarily treated with a conventional splint but ceased to use it because of the inconvenience in activities of daily living.
The subjects included 10 female patients (mean age = 44.2 years). The outcome was assessed using the visual analogue scale score for pain, the disabilities of the arm, shoulder and hand score, range of motion of the wrist, and the grip strength. The mean follow-up period after wearing the aluminum splint was 8.8 months.
All parameters, including the visual analogue scale pain and disabilities of the arm, shoulder and hand scores, improved significantly (p < 0.05) following use of the aluminum splint relative to the pretreatment scores. Seven patients continued to use the aluminum splint, and three of the seven had complete remission from related pain.
Constant use of the aluminum splint during the study period was associated with improvement in the ulnar-sided wrist pain scores, which reconfirmed that increased adherence to splint use in daily activities is an important intentional behavioral strategy.
Although the custom splint is effective for alleviation of wrist pain in ulnocarpal abutment syndrome, continuity of splint use is a key element of conservative treatment. This study showed that a splint that patients were willing to wear in their daily life was a useful device for alleviation of pain.
Prosthetics and Orthotics International 07/2014; 39(6). DOI:10.1177/0309364614541459 · 1.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After traumatic spinal cord injury (SCI), endoplasmic reticulum (ER) stress exacerbates secondary injury, leading to expansion of demyelination and reduced remyelination due to oligodendrocyte precursor cell (OPC) apoptosis. Although recent studies have revealed that amiloride controls ER stress and leads to improvement in several neurological disorders including SCI, its mechanism is not completely understood. Here, we used a rat SCI model to assess the effects of amiloride on functional recovery, secondary damage expansion, ER stress-induced cell death and OPC survival. Hindlimb function in rats with spinal cord contusion significantly improved after amiloride administration. Amiloride significantly decreased the expression of the pro-apoptotic transcription factor CHOP in the injured spinal cord and significantly increased the expression of the ER chaperone GRP78, which protects cells against ER stress. In addition, amiloride treatment led to a significant decrease in ER stress-induced apoptosis and a significant increase of NG2-positive OPCs in the injured spinal cord. Furthermore, in vitro experiments performed to investigate the direct effect of amiloride on OPCs revealed that amiloride reduced CHOP expression in OPCs cultured under ER stress. These results suggest that amiloride controls ER stress in SCI and inhibits cellular apoptosis, contributing to OPC survival. The present study suggests that amiloride may be an effective treatment to reduce ER stress-induced cell death in the acute phase of SCI.
European Journal of Neuroscience 06/2014; 40(7). DOI:10.1111/ejn.12647 · 3.18 Impact Factor