LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-Catenin

Abstract

The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. In this study, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of Lats1 in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in Lats1-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. In vivo, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). β-catenin was positively correlated with YAP1 expression in vivo and in vitro. When YAP1 was strongly positive in the nucleus, β-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, β-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/β-catenin signaling pathway. This study provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-β-catenin.

Impact statement

This study demonstrated that the LATS1/YAP1 signaling axis promotes the osteogenic differentiation, proliferation, and migration of bone marrow-derived stem cells through the activation of the Wnt/β-catenin signaling pathway and provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in distraction osteogenesis through the LATS1/YAP1-β-catenin association.