BMP3抑制大鼠佐剂诱导性关节炎的炎症反应OA

Objective To investigate the effect of bone morphogenetic protein 3(BMP3)on the expression of in-flammatory factors and joint damage in adjuvant arthritis(AA)induced by Freund's complete adjuvant(FCA)in rats.Methods The AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb,and BMP3 overexpressing adenovirus(Ad-BMP3)or control adenovirus(Ad-NC)was injected in situ into the knee joint cavity on day 8 after modeling.Subsequently,HE staining was used to observe the histopatho-logical changes in the synovium,immunohistochemistry was used to detect the expression of BMP3 in the synovium,and ELISA was used to analyze the expression levels of IL-6,IL-1β and TNF-α in the serum.Primary fibroblast-like synoviocytes(FLS)were isolated from AIA rats,the expression of BMP3 in FLS was knocked down or overexpressed,and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflamma-tory factors in FLS.Results HE staining confirmed the successful establishment of the AIA model.Compared with normal rats,AIA rats showed decreased BMP3 expression in synovial tissue.Knockdown of BMP3 promoted the protein expression of inflammatory factors(IL-6,IL-1β,IL-17A,TNF-α)and the mRNA expression of chemo-kines[C-C motif chemokine ligand 2(CCL2),C-C motif chemokine ligand 3(CCL3),Vascular Cell Adhesion Molecule-1(VCAM-1)]in FLS.In contrast,overexpression of BMP3 suppressed the expression of these inflamma-tory factors and chemokines.Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion.Conclusion BMP3 sup-presses the production of inflammatory factors and chemokines in FLS,thereby alleviating synovial hyperplasia and bone erosion in arthritis.