Periodic Heat Stress Licenses EMSCs Differentiation Into Osteoblasts via YAP Signaling Pathway Activation

Abstract BackgroundThe repair and regeneration of large bone defects represent a highly challenging task for bone tissue engineering. Although recent studies have shown that osteogenesis is stimulated by periodic heat stress, the thermal regulation of the osteogenic differentiation of ectomesenchymal stem cells (EMSCs) is not well studied. Methods and resultsIn this study, the direct effects of periodic heat stress on the differentiation of EMSCs into osteoblasts were investigated. EMSCs derived from rat nasal respiratory mucosa were seeded in culture plates, followed by 1 h of heat stress at 41 °C every 7 days during osteogenic differentiation. Based on the results of the present study, periodic heating increases alkaline phosphatase (ALP) activity, upregulates osteogenic-related proteins and promotes EMSC mineralization. In particular, increased YAP nuclear translocation and YAP knockdown inhibited osteogenic differentiation induced by heat stress. Furthermore, the expression and activity of transglutaminase 2 (TG2) were significantly increased after YAP nuclear translocation. ConclusionTogether, these results indicate that YAP plays a key role in regulating cellular proteostasis under stressful cellular conditions by modulating the TG2 response.