Cordycerebroside A suppresses VCAM-dependent monocyte adhesion in osteoarthritis synovial fibroblasts by inhibiting MEK/ERK/AP-1 signaling

Osteoarthritis (OA) is characterized by the infiltration and adhesion of monocyte into the joint synovium. Vascular cell adhesion molecule 1 (VCAM-1) is a critical cell adhesion molecule that controls monocyte motility during OA progression. Cordycerebroside A, a cerebroside compound isolated from Cordyceps militaris, inhibits the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in synovial macrophages, but has not yet been investigated in OA. Gene Expression Omnibus (GEO) dataset analysis revealed higher levels of VCAM-1 and CD11b (a monocyte marker) in OA synovial tissue compared with normal healthy tissue. The same results were observed in anterior cruciate ligament transaction (ACLT)-induced OA in rats compared with normal healthy controls. Cordycerebroside A markedly suppressed VCAM-1 expression and monocyte adhesion in human OA synovial fibroblasts. The MEK, ERK and AP-1 signaling cascades regulated cordycerebroside A-induced inhibition of VCAM-1 production. Thus, cordycerebroside A is a promising agent for the treatment of OA.