Bone morphogenetic proteins for articular cartilage regeneration.

Degeneration of articular cartilage (AC) tissue is the most common cause of osteoarthritis (OA) and rheumatoid arthritis. Bone morphogenetic proteins (BMPs) play important roles in bone and cartilage formation. This article reviews the experimental and clinical applications of BMPs in cartilage regeneration. Experimental evidence indicates that BMPs play an important role in protection against cartilage damage caused by inflammation or trauma, by binding to different receptor combinations and, consequently, activating different intracellular signaling pathways. Loss of function of BMP-related receptors contributes to the decreased intrinsic repair capacity of damaged cartilage and, thus, the multifunctional effects of BMPs make them attractive tools for the treatment of cartilage damage in patients with degenerative diseases. However, the development of BMP therapy as a treatment modality for cartilage regeneration has been hampered by certain factors, such as the eligibility of participants in clinical trials, financial support, drug delivery carrier safety, availabilities of effective scaffolds, appropriate selection of optimal dose and timing of administration, and side effects. Further research is needed to overcome these issues for future routine clinical applications. Research and development leading to the successful application of BMPs can initiate a new era in the treatment of cartilage degenerative diseases like OA.

Electrical stimulation for pain relief in knee osteoarthritis: systematic review and network meta-analysis.

OBJECTIVE: To investigate the efficacy of different electrical stimulation (ES) therapies in pain relief of patients with knee osteoarthritis (OA). METHOD: Electronic databases including MEDLINE, Embase and Cochrane Library were searched through for randomized controlled trials (RCTs) comparing any ES therapies with control interventions (sham or blank) or with each other. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment effectiveness. RESULTS: 27 trials and six kinds of ES therapies, including high-frequency transcutaneous electrical nerve stimulation (h-TENS), low-frequency transcutaneous electrical nerve stimulation (l-TENS), neuromuscular electrical stimulation (NMES), interferential current (IFC), pulsed electrical stimulation (PES), and noninvasive interactive neurostimulation (NIN), were included. IFC is the only significantly effective treatment in terms of both pain intensity and change pain score at last follow-up time point when compared with the control group. Meanwhile, IFC showed the greatest probability of being the best option among the six treatment methods in pain relief. These estimates barely changed in sensitivity analysis. However, the evidence of heterogeneity and the limitation in sample size of some studies could be a potential threat to the validity of results. CONCLUSION: IFC seems to be the most promising pain relief treatment for the management of knee OA. However, evidence was limited due to the heterogeneity and small number of included trials. Although the recommendation level of the other ES therapies is either uncertain (h-TENS) or not appropriate (l-TENS, NMES, PES and NIN) for pain relief, it is likely that none of the interventions is dangerous. LEVEL OF EVIDENCE: LevelⅡ, systematic review and network meta-analysis of RCTs.

Effects of osteopontin on the expression of IL-6 and IL-8 inflammatory factors in human knee osteoarthritis chondrocytes.

OBJECTIVE: Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by progressive destruction of articular cartilage, OA lead to chronic pain and functional restrictions in affected joints. The present study was to investigate the role of osteopontin (OPN) in the athogenesis of OA through studying the effect of OPN on expression of IL-6 and IL-8 inflammatory factors in human OA chondrocytes. PATIENTS AND METHODS: One-step type II collagenase digestive method was used to isolate OA chondrocytes from sectional cartilage specimens of 16 primary knee OA patients received total knee replacement surgery. Synchronized first-generation chondrocytes were then treated with OPN (100 ng/ml or 1 µg/mL). The changes in cell morphology of OA chondrocytes were analyzed before and after treated with OPN; and the expression levels of IL-6 and IL-8 were evaluated by real-time q-PCR. RESULTS: Chondrocytes were successfully isolated from human OA knee cartilage, and the viability of isolated chondrocytes was 92.11±3.13%. Adherent chondrocytes formed clusters of irregular polygonal shape with intercellular pseudopodia extension. After OPN treatment, cells became fusiform or irregularly shaped, and the number of intercellular pseudopodia decreased significantly. The mRNA expression of IL-6 increased to 1.83 times at 0.1 µg/ml of OPN and 3.1 times at the dose of 1 µg/ml; the expression of IL-8 increased to 1.57 and 3.27 times at the dose of 0.1 µg/ml and 1 µg/ml respectively. CONCLUSIONS: OPN could up-regulate expression of IL-6 and IL-8 cytokines in human OA chondrocytes, and the expression increased with the increasing concentration of OPN, which might be one of the potential mechanisms of OPN in the development of OA.

Effectiveness of continuous and pulsed ultrasound for the management of knee osteoarthritis: a systematic review and network meta-analysis.

BACKGROUND: To investigate the efficacy of continuous and pulsed ultrasound (US) in the management of knee osteoarthritis (OA). DESIGN: This systematic review and network meta-analysis covered 12 trials in total. Electronic databases including MEDLINE, Embase and Cochrane Library were searched through to identify randomized controlled trials comparing the two modes of US with control interventions (sham or blank) or with each other. Bayesian network meta-analysis was used to integrate both the direct and indirect evidences on treatment effectiveness. RESULTS: Pulsed US (PUS) is more effective in both pain relief and function improvement when compared with the control group; but for continuous US (CUS), there is only a significant difference in pain relief in comparison with the control group. In addition, no matter in terms of pain intensity or function at the last follow-up time point, PUS always exhibited a greater probability of being the preferred mode. However, the evidence of heterogeneity and the limitation in sample size of some studies could be a potential threat to the validity of results. CONCLUSIONS: Our findings indicated that PUS, with a greater probability of being the preferred mode, is more effective in both pain relief and function improvement when compared with the control group. However, CUS could only be considered as a pain relief treatment in the management of knee OA. The findings also confirmed that none of these modes is dangerous. LEVEL OF EVIDENCE: Level II, systematic review and network meta-analysis of randomized controlled trials.

Usefulness of specific OA biomarkers, thrombin-cleaved osteopontin, in the posterior cruciate ligament OA rabbit model.

OBJECTIVE: We undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model. METHOD: PCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay. RESULTS: The macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P < 0.001) and were elevated peaking at 24 weeks (P < 0.00001) after PCLT compared to baseline. A positive significant correlation was found between thrombin-cleaved OPN levels and the macroscopic scores (8 weeks: ρ = 0.695, P = 0.012; 16 weeks: ρ = 0.751, P = 0.005; 24 weeks: ρ = 0.660, P = 0.020). Furthermore, the same correlation was noted between thrombin-cleaved OPN levels and the histological scores (4 weeks: ρ = 0.609, P = 0.036; 8 weeks: ρ = 0.662, P = 0.019; 16 weeks: ρ = 0.827, P = 0.001; 24 weeks: ρ = 0.813, P = 0.001). CONCLUSION: In this rabbit model of PCLT, thrombin-cleaved OPN levels in SF appear to provide a useful marker of OA disease severity and progression.

Treatment of trochanteric fractures with proximal femoral nail antirotation or dynamic hip screw systems: a meta-analysis.

OBJECTIVE: A meta-analysis to compare the intraoperative and postoperative outcome data for the proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) implant systems for the treatment of patients with trochanteric fractures. METHODS: A detailed search of several electronic databases was undertaken to identify randomized controlled trials published before 5 December 2011 that compared PFNA with DHS in patients with trochanteric fractures. RESULTS: A quantitative meta-analysis of 11 studies including 798 patients was performed. PFNA was associated with significant reductions in duration of surgery (weighted mean difference [WMD] -21.38 min; 95% confidence interval [CI] -33.50, -9.26 min), intraoperative blood loss (WMD -176.36 ml; 95% CI -232.20, -120.52 ml), rate of fixation failure (relative risk [RR] 0.27, 95% CI 0.11, 0.62) and rate of postoperative complications (RR 0.46; 95% CI 0.31, 0.70) compared with DHS. CONCLUSION: The use of PFNA for treatment of trochanteric fractures was found to be superior to DHS in terms of the duration of surgery, intraoperative blood loss, and rates of fixation failure and overall complications.

Elevated osteopontin level of synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis patients.

OBJECTIVE: To investigate osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and their relationship with severity of the disease. METHOD: Fifty patients aged 48-81 years with knee OA and 10 healthy controls were enrolled in this study. Anteroposterior knee radiographs or/and Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. RESULTS: Compared to healthy controls, OA patients had higher OPN concentration in synovial fluid (4519.60+/-1830.37, 95%CI 3999.42-5039.79 vs 1179.70+/-303.39, 95%CI 1035.53-1438.74 pg/ml, P<0.001)and articular cartilage(0.6+/-0.06, 95%CI 0.59-0.62 vs 0.43+/-0.07, 95%CI 0.38-0.48, P<0.01). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411, 95%CI 0.150-0.619, P=0.003). Subsequent analysis showed that synovial fluid OPN levels significantly correlated with severity of disease (Spearman's rho=0.581, 95%CI 0.335-0.726, P<0.001). Furthermore, the articular cartilage levels of OPN also correlated with disease severity (Spearman's rho=0.675, 95%CI 0.500-0.808, P<0.001). CONCLUSIONS: OPN in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA.

[Optimized linear temperature programming for capillary gas chromatography by the method of gridding search].

Linear temperature programming of capillary gas chromatography was optimized by using a new method of gridding search. A point of gridding demonstrated a condition of temperature programmed and the resolution and the retention time were optimized at all gridding points. With a new design of calculation, the method not only considered directly all components that were separated, but the velocity of calculation was improved also. Twenty-one compounds of alkanes, alcohols, halo-hydrocarbons and aromatic hydrocarbons, of which Kovats Indexes are varying from 600 to 1,000, were separated by this new method on an OV-101 column under linear temperature programming. Good results were obtained. The time for optimizing the 21 compounds was less than 1 min.

[Myelopathy-hand and cervical spondylotic myelopathy].

The clinical manifestations and MRI characteristics of 58 patients with cervical spondylotic myelopathy were analysed in this study. The results showed that there was myelopathy-hand in 49 patients and none in 9 patients. Two groups were not significantly different in gender, age, course and involved segment, side or level of spinal cord(P > 0.05), but were significantly different in the compression degree of spinal cord(P < 0.01). In the positive group, the degree of myelopathy-hand was positively related to the severity of spastic gait, pyramidal tract sign and spinal cord compression.

[Effects of receptor-mediated endocytosis on macrophage membrane potential, cytosolic pH and lysosomal pH].

The effects of Con A, WGA, Zymosan A on membrane potential, cytosolic pH and lysosomal pH of cultured mouse macrophages were measured with fluorescence method. The results showed all the three kinds of ligands caused macrophage membrane potential hyperpolarization, cytosolic acidification and lysosomal alkalization, but reached their stabilized conditions at different times. The acidification of cytosl might inhibit further endocytosis. Alkalization of lysosomes was a basic factor for exocytosis of lysosomal contents. These receptor-mediated induced changes reflected cellular self-regulation and self-protection.

[Receptor-mediated endocytosis induced macrophage cytosolic acidification and exocytosis].

The effects of Con A, WGA, Zymosan A on macrophage cytosolic pH and outflow of lysosomal content through exocytosis were studied with SNAFL-calcein and FITC-Dextran on ACAS570. The results showed all three ligands could induce macrophage cytosolic acidification in about 10 min and kept at the same level hereafter; outflow of lysosomal fluorescent probe through exocytosis appeared in 15-20 min. In resting conditions, macrophage lysosomes mainly distributed in cell center; after stimulated for 15 min by three ligands, the number of lysosomes increased in membrane periphery, in 25-30 min lysosomes moved back toward cell center. We proposed that ligands induced lysosomal pH rises was a basic factor for outflow of lysosomal content through exocytosis, cytosolic acidification inhibited receptor-mediated endocytosis. Cytosolic acidification and outflow of lysosomal content through exocytosis were the results of cellular self-regulation and self-protection during receptor-mediated endocytosis.