Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms. Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted μCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro, the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca2+) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively. Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca2+ in a Piezo1-dependent manner. Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca2+, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model. The translational potential of this article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.