Guang-hua Lei

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

OBJECTIVEnTo 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.nnnMETHODnFifty 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.nnnRESULTSnCompared 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 (Spearmans rho=0.581, 95%CI 0.335-0.726, P<0.001). Furthermore, the articular cartilage levels of OPN also correlated with disease severity (Spearmans rho=0.675, 95%CI 0.500-0.808, P<0.001).nnnCONCLUSIONSnOPN 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.

Efficacy of platelet-rich plasma combined with allograft bone in the management of displaced intra-articular calcaneal fractures: a prospective cohort study.

To investigate whether platelet‐rich plasma (PRP) when used with allograft bone improves the management outcome of displaced intra‐articular calcaneal fractures. Over a 7‐year period, all displaced type III calcaneal fractures admitted in our department (276 fractures in 254 patients) were randomly divided into three groups according to the plan of management: autograft alone (nu2009=u2009101), allograft combined with PRP (nu2009=u200985), or allograft alone (nu2009=u200990). Radiographic imaging and three‐dimensional computed tomography were used to assess the thalamic portion, Bohlers angle, the crucial angle of Gissane, and the height, width and length of the calcaneum. The American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hind‐foot scoring system was used to evaluate the hind foot function at 12, 24, and 72 months postsurgery. At 12 months no significant difference existed in outcome amongst the treatment groups (pu2009>u20090.05). However, at 24 and 72 months the results of the autograft, and the allograft combined with PRP, were similar and both were significantly better than that of the allograft alone (pu2009<u20090.05). PRP augmented the favorable outcome of allografts in the management of displaced calcaneal fractures, and matched that of autograft used alone. The findings of this study thus support the clinical use of PRP in conjunction with allograft in the treatment of displaced intra‐articular calcaneal fractures.

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

BACKGROUNDnTo investigate the efficacy of continuous and pulsed ultrasound (US) in the management of knee osteoarthritis (OA).nnnDESIGNnThis 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.nnnRESULTSnPulsed 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.nnnCONCLUSIONSnOur 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.nnnLEVEL OF EVIDENCEnLevel II, systematic review and network meta-analysis of randomized controlled trials.

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

OBJECTIVEnTo investigate the efficacy of different electrical stimulation (ES) therapies in pain relief of patients with knee osteoarthritis (OA).nnnMETHODnElectronic 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.nnnRESULTSn27 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.nnnCONCLUSIONnIFC 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.nnnLEVEL OF EVIDENCEnLevelⅡ, systematic review and network meta-analysis of RCTs.

A novel hypothesis: The application of platelet-rich plasma can promote the clinical healing of white-white meniscal tears

Summary The white-white tears (meniscus lesion completely in the avascular zone) are without blood supply and theoretically cannot heal. Basal research has demonstrated that menisci are unquestionably important in load bearing, load redistribution, shock absorption, joint lubrication and the stabilization of the knee joint. It has been proven that partial or all-meniscusectomy results in an accelerated degeneration of cartilage and an increased rate of early osteoarthritis. Knee surgeons must face the difficult decision of removing or, if possible, retaining the meniscus; if it is possible to retain the meniscus, surgeons must address the difficulties of meniscal healing. Some preliminary approaches have progressed to improve meniscal healing. However, the problem of promoting meniscal healing in the avascular area has not yet been resolved. The demanding nature of the approach as well as its low utility and efficacy has impeded the progress of these enhancement techniques. Platelet-rich plasma (PRP) is a platelet concentration derived from autologous blood. In recent years, PRP has been used widely in preclinical and clinical applications for bone regeneration and wound healing. Therefore, we hypothesize that the application of platelet-rich plasma for white-white meniscal tears will be a simple and novel technique of high utility in knee surgery.

Association of osteopontin with osteoarthritis

The joint disease osteoarthritis (OA) is the most common form of arthritis, which mainly affects the older people. OA is becoming one of the major non-fatal health burdens of the world. The etiology of OA is mostly unclear, and it cannot be cured totally. Osteopontin (OPN) is a multifunctional phosphoprotein, of which overexpression and high level of presence in synovial fluid and articular cartilage were found to be associated with OA progression. Usually, in OA progression, OPN plays important role as an intrinsic regulator. Recent studies have taken attempt to use this protein as a diagnostic marker of OA and use OPN as a target for the drug development against OA. This review summarizes the role of OPN in OA, with focusing on the mechanism of action, and also discussing the diagnostic and therapeutic aspects of OA related to OPN.

Bone turnover in passive smoking female rat: relationships to change in bone mineral density

BackgroundMany studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat.MethodsForty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats.ResultsBMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats.ConclusionOur data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat.

Phosphorylation of osteopontin in osteoarthritis degenerative cartilage and its effect on matrix metalloprotease 13

The purpose of this study is to observe the differences of osteopontin (OPN) phosphorylation in osteoarthritis (OA) cartilage and normal cartilage, and evaluate the possible correlations between the OPN phosphorylation and MMP-13 expression. Degenerative cartilage (nxa0=xa029) and normal cartilage (nxa0=xa010) were identified by hematoxylin-eosin, safranin-O staining and modified Mankin score. The phosphorylation level of OPN in OA cartilage and normal cartilage was detected by immunoprecipitation. Chondrocytes were treated with phospho-OPN, OPN or buffer. Quantitative reverse transcription polymerase chain reaction (qPCR) and ELISA were used to assess the expression of MMP-13 in different treatments. The OD values of phosphorylation of OPN in normal cartilage and OA cartilage were 137.89xa0±xa010.59 and 153.52xa0±xa08.80, respectively, (Pxa0=xa00.000). Chondrocytes treated with OPN showed a higher MMP-13 expression at gene and protein level compared with control group. Chondrocytes treated with phospho-OPN showed the highest MMP-13 expression in gene and protein. In conclusion, our results revealed a higher phosphorylation level of OPN in OA cartilage than in normal cartilage. We found OPN leads to elevated expression of MMP-13 (both at gene level and protein level), and phospho-OPN had a more obvious upregulation effect on MMP-13 expression than nonphospho-OPN. Further studies are needed to reveal the mechanism of OPN phosphorylation on cartilage degeneration.

The effect of hyaluronic acid on osteopontin and CD44 mRNA of fibroblast-like synoviocytes in patients with osteoarthritis of the knee

The aim of this study was to investigate the effect of hyaluronic acid (HA) on the expression of osteopontin (OPN) and CD44 mRNA of fibroblast-like synoviocytes (FLS) in the patients with osteoarthritis (OA) of the knee. FLS were obtained from the knees of 10 patients with OA. Real-time quantitative polymerase chain reaction (Q-PCR) was used to assess the expression of the OPN mRNA and CD44 mRNA. The relative OPN mRNA expression in HA group (6.47xa0±xa02.30-fold) was significantly higher than in the control group (Pxa0=xa00.045, Pxa0<xa00.05), while in HYL group (0.65xa0±xa00.21-fold) it was lower than in the control group (Pxa0=xa00.037, Pxa0<xa00.05), and the difference in OPN mRNA expression between HA group and HYL group also showed statistically significant (Pxa0=xa00.001, Pxa0<xa00.05); however, there was no significant difference between each group of the relative CD44 mRNA expression (Pxa0>xa00.05). Our study showed that HA can upregulate OPN mRNA expression in OA fibroblast-like synoviocytes, and the high expression of OPN mRNA in OA may be a result of increased HA level of OA synovitis; however, HA cannot affect the CD44 mRNA expression in OA fibroblast-like synoviocytes, and the high expression of CD44 mRNA in OA may be not a result of increased HA level of OA synovitis.

Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis

ObjectivesTo investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease.MethodsAll 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods.ResultsCD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (Pxa0<xa00.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρxa0=xa0−0.848, Pxa0<xa00.01).ConclusionsCD44 in articular cartilage is associated with progressive knee OA joint damage.