Apelin-13 activates the BMP4/SMAD pathway through APJ to enhance osteoblastic differentiation and mineralization.

Osteoblastic differentiation and mineralization are essential processes for bone formation and remodeling. Apelin, an endogenous ligand for the Apelin receptor (APJ), has been involved in various physiological functions, however, its function in osteogenesis remains unclear. The present research was dedicated to exploring the impacts of Apelin-13 on the osteoblastic differentiation process within MC3T3-E1 cells. The results showed that APJ expression was upregulated during osteogenic induction. Apelin-13 greatly increased the expression of osteogenic markers ALP, OCN, OPN, and Col1A1, promoted ALP activity and mineralization, and raised RUNX-2 expression at both mRNA and protein levels. Furthermore, Apelin-13 activated the BMP4/SMAD1/5/8 signaling pathway. These effects were abolished by LDN193189, a specific inhibitor of BMP signaling, and by APJ knockdown, indicating that Apelin-13 exerts its pro-osteogenic effects through APJ via the BMP4/SMAD pathway.