Paeoniflorin elevates the expression of SOCS3 in macrophages to prevent MIA-induced osteoarthritis in mice

Abstract Osteoarthritis (OA) is a degenerative joint disease that occurs frequently in the middle aged and elderly population, limiting the joint function and disability with severe pain. However, there are limited treatments that can simultaneously relief pain. Paeoniflorin is isolated from Chinese-medicine Paeonia lactiflora with anti-inflammation and immunomodulatory effects. Here we investigated the efficacy and possible mechanisms of paeoniflorin to attenuate pain, inflammation and cartilage degradation in an OA mouse model. The analgesic effect of paeoniflorin was studied by measuring allodynia with von Frey Hairs. H&E staining was used to detect structural integrity and inflammation of joint tissues. RAW264.7 was used to investigate the effect of paeoniflorin on related signaling pathway and on reflexivity of lipopolysaccharide (LPS)-induced inflammation through western blot. Paeoniflorin relieved mechanical allodynia and reduced cartilage degeneration in vivo. Meanwhile paeoniflorin could upregulate Gas6 expression, activate Axl receptors, upregulate suppressor of cytokine signaling3 (SOCS3) expression, inhibit MMP-9 expression and decrease p38 phosphorylation in joints. Cell experiments showed that paeoniflorin regulated Gas6-TAM pathway via ERK signal and decreased MMP-9 expression and M1 polarization in vitro . Paeoniflorin may inhibit joint inflammation and relieve pain via upregulating Gas6-TAM pathway and macrophage M2 polarization, which may be a potential treatment for osteoarthritis.