YAP balances the osteogenic and adipogenic differentiation of hPDLSCs in vitro partly through the Wnt/β-catenin signaling pathway

Linglu Jia, Yunpeng Zhang, Yawen Ji, Yixuan Xiong, Wenjing Zhang, Yong Wen, Xin Xu
Biochemical and Biophysical Research Communications 2019 August 14
Human periodontal ligament stem cells (hPDLSCs) are potential seed cells for bone tissue engineering, but the molecular regulatory mechanisms of their multi-differentiation remain unclear. Here, we found that Yes-associated protein (YAP), a transcriptional coactivator in Hippo signaling pathway, regulated the multi-differentiation ability of hPDLSCs: overexpressing YAP contributed to an enhancement of osteogenic differentiation and a decrease in adipogenic differentiation, while knocking down YAP inhibited the osteogenic differentiation and promoted the adipogenic differentiation of hPDLSCs. In addition, YAP promoted the stabilization and nuclear transfer of β-catenin in hPDLSCs, probably through regulating several upstream proteins of the Wnt/β-catenin signaling pathway, including LRP6 and DVL3. Treatment with DKK1 or Wnt3a reversed the effects of overexpressing or knocking down YAP on non-phospho β-catenin (stabilized β-catenin) and cell differentiation. Taken together, YAP promoted osteogenic and inhibited adipogenic differentiation of hPDLSCs in vitro, which was partly via LRP6 and DVL3 mediated Wnt/β-catenin signaling pathway. YAP could be a candidate regulatory target for facilitating the application of hPDLSCs in bone regeneration.

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