Lysophosphatidic acid-induced YAP activation regulates osteogenesis of MC3T3-E1

Lysophosphatidic acid (LPA) is a small bioactive lysophospholipid that elicits diverse biological activities in bone homeostasis and diseases. However, the specific functions of LPA and intrinsic mechanism underlying these processes is not well understood. In this study, we identified that LPA regulated cell proliferation, migration, and osteogenic differentiation primarily via LPA₁ in MC3T3-E1 pre-osteoblastic cells. More importantly, western blot analysis indicated that LPA stimulated the activation of the transcriptional regulator YAP via the Hippo pathway kinases LATS, but had negligible effects on MST. Moreover, verteporfin was applied to block YAP, which further elucidated the effects of LPA-induced YAP activation on osteogenesis. Interestingly, Rho-kinase (ROCK) might also be involved in LPA-induced YAP nuclear localization and dephosphorylation. Taken together, these data provide novel insights into the molecular mechanisms of LPA in bone homeostasis and regeneration.