Therapeutic efficacy of cyclosporin A against spinal cord injury in rats with hyperglycemia.

The present study aimed to explore the therapeutic effects of cyclosporin A (CsA) on spinal cord injury (SCI) in rats with hyperglycemia and to identify a novel potential method to treat SCI in the presence of hyperglycemia. Female Sprague­Dawley (SD) rats were randomly allocated into four groups: Sham, SCI, SCI+hyperglycemia and SCI+hyperglycemia+CsA groups. Streptozotocin­induced hyperglycemic SD rats and a weight­drop contusion SCI model were established. The Basso, Beattie, Bresnahan scale and inclined plane test were used to evaluate the neurological function of the rats. Flow cytometric assay was performed to detect the apoptotic rates of cells in the spinal cord. ELISA and western blot analysis were performed to determine the levels of interleukin (IL)­10, tumor necrosis factor (TNF)­α, cyclophilin­D (Cyp­D) and apoptosis­inducing factor (AIF). The results demonstrated that CsA significantly improved the neurological function of the SCI rats with hyperglycemia. CsA markedly reduced the number of apoptotic cells exaggerated by hyperglycemia in the spinal cord of the SCI rats. CsA significantly decreased the expression levels of IL­10, TNF­α, Cyp­D and AIF in the spinal cord of the SCI rats. Overall, the present study revealed a significant role of CsA in the treatment of SCI in the presence of hyperglycemia by inhibiting the apoptosis of spinal cord cells.

The association between parathyroid hormone 1­34 and the Wnt/ß­catenin signaling pathway in a rat model of osteoarthritis.

The aim of the current study was to determine the effect of parathyroid hormone (PTH) 1­34 on cartilage degeneration, and the association between PTH 1­34 and factors associated with the Wnt/ß­catenin pathway following anterior cruciate ligament and medial meniscectomy­induced osteoarthritis (OA) in rats. A total of 64 Sprague­Dawley rats were randomly divided into the following four groups: Sham­operated rats with normal saline (NS)­treatment (n=16); anterior cruciate ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS­treatment (n=16); sham­operated rats treated with PTH 1­34 (n=16); and ACLT + MMx rats treated with PTH 1­34 (n=16). PTH (15 µg/kg/day) was administered via subcutaneous injection 5 days per week from the first postoperative day for 2 or 6 weeks. Staining with hematoxylin and eosin and safranin O, and a scoring system modified by Mankin were used to assess the histopathological features of cartilage. The present study detected the expression of PTH 1 receptor (PTH1R), sclerostin, dickkopf Wnt signaling pathway inhibitor 1 (DKK1), ß­catenin and runt­related transcription factor 2 (RUNX2) in cartilage by immunohistochemical analysis to determine the association between PTH 1­34 and factors associated with the Wnt/ß­catenin pathway. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was performed to detect the mRNA expression levels of PTH1R and ß­catenin in cartilage. Histological analysis demonstrated that cartilage degeneration was present post­surgery and gradually increased over time. PTH 1­34 reduced the Mankin scores in ACLT + MMx rats compared with the NS­treated ACLT + MMx rats. Immunohistochemistry and RT­qPCR analysis demonstrated that, in cartilage, PTH 1­34 treatment increased the mRNA expression and protein levels of PTH1R and ß­catenin, and decreased protein levels of sclerostin, DKK1 and RUNX2 in ACLT + MMx rats compared with the NS­treated ACLT + MMx group. The present study demonstrated that PTH 1­34 upregulated the Wnt/ß­catenin signaling pathway and that PTH1­34 downregulated RUNX2 through an alternative pathway to the Wnt/ß­catenin signaling pathway, in a rat model of OA.

Detection of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis patients undergoing total knee arthroplasty.

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disorder and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is regarded as a serological marker for diagnosing early and late RA. In the present study, we aimed to determine the levels of anti-CCP Ab in serum, synovial tissue (ST) and synovial fluid (SF) in RA patients undergoing total knee arthroplasty (TKA). 23 patients were included. Rheumatoid factor (RF) and anti-CCP Ab in serum were detected prior to surgery and then at 1, 3, 6 and 12 months after TKA. Synovial samples were obtained by knee arthroscopy and used for anti-CCP detection. One month after TKA, anti-CCP levels were significantly reduced (P < 0.01) in RA patients. However, their levels were not significantly different between pre-surgery and 1 year post-surgery (P > 0.05). Furthermore, anti-CCP levels in ST were much higher than in serum. These findings suggest that RA patients should continue antirheumatic therapy after TKA. ST is the preferred place for the synthesis of anti-CCP Ab.

[Association of single nucleotide polymorphisms (SNPs) in leptin receptor gene with knee osteoarthritis in the Ningxia Hui population].

To investigate the association between primary knee osteoarthritis (OA) and single nucleotide polymorphism (SNP) (A668G) of leptin receptor gene (LEPR) in the Ningxia Hui population. A case-control association study has been adopted in this thesis. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were performed to investigate the SNP of A668G site within LEPR from 148 patients with knee OA and 155 controls (asymptomatic and radiographically negative) with matched age and gender among Ningxia Hui population. In addition, genotypes of LEPR were verified by direct sequence analysis on PCR products. The result indicates that allele and genotype frequencies (P=0.024 and 0.008, respectively) in LEPR SNP A668G were significantly different in the knee OA patients group and control group, and in the knee OA patients group, the serum levels of leptin decreased significantly (P<0.001) and the serum levels of soluble leptin receptor increased significantly (P<0.001) compared with control group. Therefore, LEPR SNP A668G is associated with susceptibility to knee OA, which would be used as the genetic marker in predicting the risk of knee OA and would be one of the candidate genes in early prevention and control.

Association between the +104T/C polymorphism in the 5'UTR of GDF5 and susceptibility to knee osteoarthritis: a meta-analysis.

Although the +104T/C polymorphism in the 5' untranslated region (UTR) of growth differentiation factor 5 (GDF5) plays a role in the pathogenesis of knee osteoarthritis, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association of +104T/C polymorphism with knee osteoarthritis. Published literature from PubMed, Google Scholar and China National Knowledge Infrastructure data was retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 6 case-control studies containing 2,744 patients and 4,518 controls were enrolled in this meta-analysis. Overall, a statistically significant association was found between the +104T/C polymorphism and risk of knee osteoarthritis (TT vs. CC: OR 1.68, 95% CI=1.41-2.01; TT vs. TC: OR 1.18, 95% CI=1.01­1.38; dominant model: OR 0.72, 95% CI=0.61-0.86). Taking into account the effect of ethnicity, further stratified analyses were performed. In the subgroup analysis, the same association was identified in Caucasian (TT vs. CC: OR 1.45, 95% CI=1.13-1.85) and Asian (TT vs. CC: OR 1.99, 95% CI=1.53­2.60; TT vs. TC: OR 1.33, 95% CI=1.16-1.52; dominant model: OR 0.64, 95% CI=0.56-0.72; recessive model: OR 1.77, 95% CI=1.37-2.29) populations. The meta-analysis results demonstrated that the +104T/C polymorphism in the 5'-UTR of GDF5 is associated with risk of knee osteoarthritis.

[A analysis on the effect of with or without patellar replacement in total knee arthroplasty].

OBJECTIVE: To evaluate the outcome of total knee arthroplasty with or without resurfacing of the patella with particular attention to knee score, knee function score and incidence of postoperative anterior knee pain, providing the basis for the choice of surgical procedure. METHODS: CNKI, PubMed, ScienceDirect, Highwire and other databases were searched for the randomized controlled trials relevant to the patellar with or without replacement in total knee replacement arthroplasty between 1998 and 2010, evaluating of the methodological quality of included studies and extracting valid data. RESULTS: The 80 citations were identified as related to patellar resurfacing during total knee arthroplasty, 13 articles meet all inclusion criteria for this study. The incidence of postoperative anterior knee pain is greater in knees without replaced patellas (RR = 0.78, 95%CI: 0.61 - 0.99, P = 0.04). No differences are observed between the 2 groups for knee score and knee function score. Knee score (WMD = -0.49, 95%CI: -1.79 - 0.81, P = 0.46), knee function score (WMD = 1.10, 95%CI: -1.77 - 3.98, P = 0.45). CONCLUSIONS: The patella replacement can significantly reduce the incidence of postoperative anterior knee pain. There is no difference in the knee score and knee function score between two groups.

[Significance and role of increased expression of extracellular matrix metalloproteinase induced in the aseptic loosening of prostheses].

OBJECTIVE: To investigate the expression of extracellular matrix metalloproteinase induced (EMMPRIN) in the interface tissue, and explore the role of EMMPRIN in the aseptic loosening of prostheses. METHODS: Immunohistochemistry was performed to characterize the EMMPRIN-expressing cells at sites of interface tissue around aseptic loosened hip prostheses in 16 cases. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to study the existence of EMMPRIN mRNA in interface tissue samples. And it was followed up by computer assisted image analysis in order to detect the A values of their expression. Synovium of hip joint of 8 femoral neck fracture were in control group. RESULTS: Strong immunostaining of EMMPRIN was found in the macrophages and fibroblasts of lining-like layers and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. Expression of EMMPRIN was significantly higher in interface tissue than the control synovium (z=-3.252, P=0.001). RT-PCR of interface tissue samples disclosed the presence of EMMPRIN mRNA of 14 cases. In interface tissue, the A value of EMMPRIN increased significantly compared to control synovium (P<0.01). CONCLUSION: Over-expression of EMMPRIN up-regulates the production of matrix metalloproteinase (MMPs) in the interface tissue. And it can promote the bone destruction around prostheses. Thereby it may be one of methods to prevent and treat aseptic loosening of prostheses by repression the biology activity of EMMPRIN.