Distinct osteogenic effect of different periosteum derived cells via Hippo-YAP cascade signaling

Abstract

ABSTRACT Periosteum is expected for bone repairing due to excellent regenerative potential. PDCs are the main source of cells for promoting bone repair. However, PDCs from different sites have been confirmed to be site specific due to their distinct embryonic origin and the methods of bone formation. Hippo-YAP pathway is proved to play a critical role in fate decision of mesenchymal stem cells. The effect of Hippo-YAP on PDCs has not been reported so far. Hence, we aim to explore the differences of PDCs from mandible and femur along with their possible responses to YAP signaling. mPDCs and fPDCs were obtained and tested through flow cytometry for identification. Follow-up results illustrated mPDCs was cubic shape and with better proliferation while fPDCs preferred slender cell shape with worse cell viability compared with mPDCs. mPDCs was superior to fPDCs in ALP activity, related mRNA expression and calcium deposits in late stage. Interestingly, downregulation of YAP promoted the ALP activity, related mRNA expression and calcium deposits of fPDCs while hindered that of mPDCs in vitro. Moreover, implant animal model in mandible and femur were constructed for evaluation in vivo. Histological results were similar to the results in vitro. We speculate this may result from their different embryonic origin and the way of bone formation. Taken together, results available suggested that mPDCs may serve as more optimal seed cells for tissue engineering compared with fPDCs; however, considering their different response to YAP signaling, to ensure sufficient YAP expression in mPDCs and appropriate declining YAP expression in fPDCs may establish better osteogenesis.