Effect of Rb1cc1 on cartilage and subchondral bone in osteoarthritis

Purpose: To investigate the role of Rb1cc1 in cartilage and subchondral bone in the process of osteoarthritis. Methods: Eight-week-old C57 mice were randomly divided into experimental group and sham group. Mice in each group were randomly assign to three time-points of 2, 4 and 8 weeks. DMM or Sham surgery was performed as previously described. Human OA tissue specimens were obtained from patients underwent knee joint replacement. Normal controls specimens were obtained from patients with femoral neck fracture who underwent hip arthroplasty. Histological staining was used to assess OA severity and immunofluorescence was used in rb1cc1 evaluation. The effects of rb1cc1 on cartilageand subchondral bone was determined in IL-1β-treated mouse chondrocytes and stress-loaded osteoblast in vitro. Interfering with the expression of rb1cc1 by transfection of siRNA. RT-PCR and western blot analyses were conducted to detect the relative expressions of protein and RNA. Results: In human samples, the expression of rb1cc1 in the OA group was significantly higher than that in the control group. In the mouse DMM model, the expression of Rb1cc1 was decreased in the 2W-DMM group and increased in the 8W-DMM group (Figure 1). In vitro, inhibition of rb1cc1 reduced catabolic (mmp13, ,mmp3) and inflammatory (iNos and cox-2) markers in chondrocytes, and decreased osteoblast-associated protein (Ocn and Alp) expression in osteoblasts (Figure 2). Conclusions: Rb1cc1 was significantly differentially expressed during OA progression. Rb1cc1 promotes catabolism and inflammatory expression in chondrocyte, and leads to osteogenic differentiation in osteoblasts. This suggests that Rb1cc1 is involved in cartilage metabolism and osteogenic metabolism in OA, which could be used as a theoretical target in bone and cartilage in OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)