Osteoarthritis (OA) is the most common chronic degenerative
joint disease, and it remains the main cause of chronic disability in elderly individuals.
Sema4D (
semaphorin 4D) is involved in the immune system and related to bone injury,
osteoporosis, osteoblast differentiation, and
rheumatoid arthritis. However, the role of
Sema4D in OA remains unclear. Hence, the LPS-stimulated chondrocyte cell injury model was constructed in this study to investigate the role of
Sema4D in OA development. The results showed that
Sema4D was increased in LPS-treated ATDC5 cells, and the knockdown of
Sema4D suppressed the decline of cell viability, the increase of cell apoptosis, and the increase of
IL-6, IL-1β, and TNF-α secretion in ATDC5 cells induced by LPS. Meanwhile,
Sema4D overexpression aggravated the cell injury triggered by LPS, and inhibiting
Plexin B1 partly abolished the effect of
Sema4D overexpression on LPS-induced chondrocyte injury. Furthermore, silencing of
Sema4D blocked the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. Enhanced
Sema4D promoted the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. What is more, inhibiting the MAPK signaling pathway abolished the promoting effect of
Sema4D overexpression on LPS-induced chondrocyte injury. Therefore, our study suggested that the knockdown of
Sema4D protects ATDC5 cells against LPS-induced injury through inactivation of the MAPK signaling pathway via interacting with
Plexin B1.