Osteoarthritis is a degenerative disease that often causes patients to experience joint pain and deformity. It has been demonstrated that tumor necrosis factor (TNF)-α is associated with the progression of osteoarthritis; however, to the best of our knowledge, the mechanisms by which TNF-α simulates the progression of osteoarthritis and the signaling pathway(s) it influences remain unknown. Therefore, the aim of the present study was to investigate the therapeutic effects of TNF-α inhibitor in an iodoacetate-induced rat model of osteoarthritis and identify its potential mechanisms of action. Western blotting, ELISA and histological analyses were performed to assess the effects of the TNF-α inhibitor on osteoarthritis. The effects of TNF-α and phosphoinositide 3-kinase (PI3K) inhibition on synovial fibroblasts isolated from rats with osteoarthritis were tested in vitro. Furthermore, the expression of various inflammatory cytokines and the PI3K/protein kinase B (AKT) signaling pathway were assessed in vitro. The results indicated that the inflammatory factors TNF-α, interleukin (IL)-1β, IL-17a and IL-8 were upregulated in synovial fibroblasts taken from rats with osteoarthritis compared with normal rats. By contrast, TNF-α inhibition downregulated IL-1β, IL-17a and IL-8 expression in synovial fibroblasts in vitro. The PI3K/AKT pathway was also upregulated in synovial fibroblasts harvested from rats with osteoarthritis compared with that in normal rats. It was demonstrated that treatment with the TNF-α inhibitor downregulated the serum and protein levels of IL-1β, IL-17a and IL-8 in rats with osteoarthritis. Furthermore, treatment with the TNF-α inhibitor also decreased matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor and ADAMTS4 expression in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the TNF-α inhibitor also inhibited the PI3K/AKT pathway in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the PI3K inhibitor ameliorated TNF-α-induced increases in IL-1β, IL-17a and IL-8 expression in synovial fibroblasts isolated from rats with osteoarthritis. Furthermore, treatment with the TNF-α inhibitor decreased inflammation, as well as joint and cartilage destruction in vivo. Taken together, the results of the present study indicate that TNF-α inhibition may downregulate the expression of inflammatory factors in synovial fibroblasts, suggesting that TNF-α inhibition may be a novel method for treating osteoarthritis by downregulating the PI3K/AKT signaling pathway.

Expression of microRNA-21 in bone tissue and serum of patients with osteoporosis (OP) and its involvement in the regulation of osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) were investigated. Bone tissue and serum were collected from 48 patients with OP and 48 normal subjects. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of six microRNAs. Among these microRNAs, the expression level of microRNA-21 in bone tissue and serum of OP patients was the lowest. In addition, BMSCs of SD rats were isolated and cultured. Subculture was performed 3 times, transfection of microRNA-21 was performed and osteogenic differentiation was induced. Control group [negative control (NC)] was transfected with microRNA-21 mimics followed by osteogenic induction. Experimental groups were transfected with microRNA-21 analogue (mimics) and microRNA-21 inhibitor (inhibitor) followed by osteogenic induction. Ten days after osteogenic induction, alkaline phosphatase (ALP) staining and alizarin red staining were performed to measure the mineralized stained area and the number of mineralized nodules in each treatment group. RT-qPCR was used to detect the expression of osteogenic genes in each group of cells. RT-qPCR results showed that microRNA-21 expression was lower in bone tissue and serum of patients with OP than that of normal subjects. Moreover, compared with control group, BMSCs showed increased stained mineralized areas, deeper color and increased number of mineralized nodules. In addition, increased mRNA expression of osteogenic genes was evident after microRNA-21 mimics transfection and osteogenic induction (p<0.05). Compared with control group, BMSCs showed decreased stained mineralized areas, lighter color, decreased number of mineralized nodules, and decreased mRNA expression of osteogenic genes after microRNA-21 inhibitor transfection and osteogenic induction (p<0.05). MicroRNA-21 is expressed at low level in bone tissue and serum in patients with OP, and microRNA-21 can promote osteogenic differentiation of BMSCs. Our study provided theoretical basis for drug treatment of OP.

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Total hip resurfacing arthroplasty (THRA) is being performed with increasing frequency for osteonecrosis of femoral head (ONFH). To evaluate femoral bone remodeling in ONFH after THRA and determine the impact of stem-neck angle (SNA) of inserted femoral component on bone remodeling, we monitored the changes in BMD in proximal femur in 23 patients with ONFH after surgery. Patients were divided into group A (SNA ! 58) and group B (SNA < 58). The BMD was measured in seven Gruen zones and two neck zones using dual-energy X-ray absorptiometry preoperatively, then at 3, 6, 12, and 24 months after surgery. At all ROIs, the BMD decreased significantly by 3 months postoperatively. The BMD ceased to decrease and reversed by 6 months. The BMD in neck increased significantly in group A, compared with group B at 24 months. The BMD increased 2% at ROI1 at 24 months in both groups, and at ROI7, the BMD in group A reversed to baseline value by 6 months and increased 5.81% at 24 months. These findings implied that the bone stock of proximal femur in ONFH can be well reserved after total hip resurfacing arthroplasty with valgus positioning of the femoral component. ß

Inhibition of bone regeneration by wear debris is the main cause of peri-prosthetic osteolysis. Here, we investigated the effect of icariin on cell proliferation, apoptosis, osteogenic differentiation and matrix mineralization of osteoblasts in an in vitro model of titanium (Ti) particle-induced osteolysis. In the present study, MC3T3-E1 cells were pretreated with 10 M icariin for 4 h and then incubated with Ti particles (0.1 mg/mL). The results showed that Ti particles inhibited cell proliferation and promoted cell apoptosis of MC3T3-E1 cells, whereas icariin pretreatment blocked the effect of Ti particles. In addition, we found that icariin stimulation alone increased ALP activity, accelerated matrix mineralization and upregulated the levels of bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and miR-21-5p; whereas, Ti particles alone exerted the opposite effects. Icariin partly reversed the effect of Ti particles on cell differentiation and mineralization. Twenty hours after transfection with antagomiR-21-5p or antagomiR-NC, the cells were pretreated with icariin for 4 h and then incubated with Ti particles. Further studies showed that partial knockdown of miR-21-5p abolished the promotion effect of icariin on osteoblast differentiation and matrix mineralization in Ti particle-stimulated MC3T3-E1 cells. In conclusion, miR-21-5p may be a potential pro-osteogenesis regulator and icariin may protect against Ti particle-induced inhibition of osteogenic differentiation and mineralization through upregulation of miR-21-5p.