Wedelolactone inhibits osteoclastogenesis but enhances osteoblastogenesis through altering different semaphorins production

Our previous study showed that wedelolactone, isolated from Ecliptae herba, enhanced osteoblastogenesis but inhibited osteoclastogenesis through Sema3A signaling pathway. This study aims to investigate the role of other semaphorins in wedelolactone-enhanced osteoblastogenesis and -inhibited osteoclastogenesis. Wedelolactone inhibited RANKL-induced Sema4D and Sema7A production, but had no effect on RANKL-reduced Sema6D expression in osteoclastic RAW264.7 cells. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone reversed osteogenic medium(OS)-reduced Sema7A expression and OS-enhanced Sema3E mRNA expression, but no effect on OS-reduced Sema3B mRNA expression. Addition of Sema4D antibody promoted wedelolactone-reduced TRAP activity and bone resorption pit formation. Wedelolactone combined with Sema4D antibody inhibited the formation of Sema4D-Plexin B1 complex. In co-culture of BMSC with RAW264.7 cells, Sema7A antibody, similar with Sema 3A antibody, reversed wedelolactone-enhanced ALP activity and mineralization level, but promoted wedelolactone-inhibited TRAP activity. However, Sema3E and Sema3B antibodies had no effect. Further, wedelolactone enhanced the binding of Sema7A with PlexinC1 and Beta1, but addition of Sema7A antibody partially blocked this binding. Our data demonstrated that wedelolactone inhibited Sema4D production and Sema4D-PlexinB1 complex formation in RAW264.7 cells, thereafter inhibiting osteoclastogenesis. At the same time, wedelolactone enhanced osteoblastogenesis through promoting Sema7A production and Sema7A-PlexinC1-Beta1 complex formation in BMSC. [Display omitted] •Several types of semaphorins are involved in wedelolactone-enhanced osteoblastogenesis and -inhibited osteoclastogenesis.•Inhibition of formation of Sema4D-PlexinB1 complex in osteoclatice RAW264.7 cells by wedelolatone.•Enhancement of Sema7A-PlexinC1-Beta1 complex formation in bone marrow mesenchymal stem cells by wedelolactone.