αCGRP affects BMSCs' Migration and Osteogenesis via the Hippo-YAP Pathway.

Alpha-calcitonin gene-related peptide (alpha CGRP) plays a significant pathophysiological role in the regulation of bone metabolism. Our previous research indicated that alpha CGRP might have a potential application in enhancing osseointegration in vivo. To further uncover the intrinsic mechanism of its networks in bone regeneration, here we investigate the impact of alpha CGRP on osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs) from both wild-type and alpha CGRP(-/-) mice. Considering the half-life of alpha CGRP in plasma is only 10 min, we applied alpha CGRP lentivirus and stably transfected it into BMSCs, followed by transfection identification and cell cycle assay. We further conducted a series of in vitro tests, and the results revealed that biological functions including migratory ability and osteogenicity exhibited positive correlation with BMSCs' alpha CGRP expression. Meanwhile, this phenomenon was associated with an enhanced expression of YAP (Yes-associated protein), the key downstream effector of the Hippo pathway. To sum up, our data together with previous in vivo observations is likely to elucidate the intrinsic mechanism of alpha CGRP in bone remodeling, and alpha CGRP would appear to be a novel treatment to promote bone wound healing.