1. Academic Validation
  2. Lysophosphatidic acid-induced YAP activation regulates osteogenesis of MC3T3-E1

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

  • Tissue Cell. 2025 Aug 28:98:103111. doi: 10.1016/j.tice.2025.103111.
Qin Zhang 1 Jiayi Liu 2 Bingfeng Wu 2 Ying Yuan 2 Ping Gong 3 Lin Xiang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral Implantology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
  • 2 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 4 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address: dentistxiang@126.com.
Abstract

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.

Keywords

Lysophosphatidic acid; MC3T3-E1; Osteogenesis; YAP.

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