LAUSR

Background We have previously reported that adiponectin (AD), an adipokine that is secreted by adipocytes, correlates closely with progressive bone erosion in rheumatoid arthritis (RA). The exact mechanism of AD towards promoting joint destruction remain unclear. Objectives Osteopontin (OPN) is required for osteoclast recruitment. We hypothesised that AD exacerbates bone erosion by inducing OPN expression in synovial tissue. This study aimed to evaluate a novel role for AD in RA. Methods The serum levels of AD and OPN were determined in 38 RA, 40 osteoarthritis (OA) patients, and 20 healthy controls using enzyme-linked immunosorbent assay (ELISA). AD and OPN production were measured by double immunofluorescence of RA and OA synovial tissue. Quantitative real-time PCR and immunofluorescence were used to evaluate the mRNA and protein expression levels of OPN in RA synovial fibroblasts (RASFs) and OA synovial fibroblasts after preincubation with AD, respectively. Migration of the RAW264.7 osteoclast precursors cell line was assessed using the Transwell migration assay and co-culture system. Bone destruction and osteoclastogenesis were assessed by immunohistochemistry, microcomputed tomography, and tartrate-resistant acid phosphatase (TRAP) staining in AD-treated collagen-induced arthritis (CIA) mice with or without OPN silencing. The expression levels of OPN and integrin αvβ3 in the ankle joint tissues of the mice were examined by double immunofluorescence. Results Our results indicated that the AD and OPN expression levels increased noticeably and were associated with each other in the RA serum. The AD distribution was coincident with that of OPN in the RA synovial tissue. AD stimulation of RASFs increased OPN production in a dose-dependent manner. AD-treated RASFs promoted RAW264.7 cell migration, and the effect was blocked with a specific antibody against OPN. Silencing of OPN using lentiviral-OPN short hairpin RNA reduced the number of TRAP-positive osteoclasts and the extent of bone erosion in the AD-treated CIA mice. When bound to integrin αvβ3, OPN functions as a mediator of AD and osteoclasts. Conclusions Our study provides new evidence of AD involvement in bone erosion. AD induces the expression of OPN, which recruits osteoclasts and initiates bone erosion. These data highlight AD as a novel target for RA treatment. Disclosure of Interest None declared