Huang Lingwei, Jiao Yiren, Xia Hangbin, Li Huili, Yu Jing, Que Yumei, Zeng Zhen, Fan Chen, Wang Chen, Yang Chen, Chang Jiang
Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China.
J Orthop Translat. 2024 Aug 13;48:146-155. doi: 10.1016/j.jot.2024.07.014. eCollection 2024 Sep.
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.
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. 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 (Ca) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively.
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 study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca in a Piezo1-dependent manner.
This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca, 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 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 Ca during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.
长期缺乏身体活动可能导致骨质疏松症和肌肉减少症并存,从而导致跌倒、骨折、残疾甚至死亡的高风险。然而,在骨质疏松症和肌肉减少症的联合治疗中,缺乏普遍适用且可行的方法。在本研究中,我们评估了硅酸锶锌生物陶瓷(SZS)提取物对骨质疏松症和肌肉减少症的影响,并探讨了其潜在机制。
在尾部悬吊大鼠模型中建立后肢骨质疏松症和肌肉减少症。对骨骼进行μCT扫描、组织学检查和基因表达分析,对肌肉进行组织学检查和基因表达分析。通过茜素红S染色、免疫荧光和qPCR确定SZS提取物对成骨细胞的作用。同样,通过免疫荧光和qPCR确定SZS提取物对成肌细胞的作用。最后,分别在MC3T3-E1和C2C12细胞中通过GsMTx4阻断Piezo1,探讨Piezo1的作用和细胞内钙离子(Ca)的变化。
我们发现SZS提取物可以同时有效地预防尾部悬吊大鼠后肢的骨结构恶化、肌肉萎缩和纤维化。研究还表明,SZS提取物可以上调Piezo1的mRNA表达,从而维持骨骼和肌肉的稳态。研究证明,SZS提取物可以通过以Piezo1依赖的方式增加细胞内Ca来促进MC3T3-E1和C2C12细胞的增殖和分化。
本研究表明,SZS提取物可以增加Piezo1介导的细胞内Ca,并促进成骨细胞的成骨分化和成肌细胞的成肌分化,有助于减轻尾部悬吊大鼠模型中的骨质疏松症和肌肉减少症。
当前的研究可能为基于生物活性陶瓷治疗肌肉骨骼疾病提供一种普遍适用且有效的策略。Piezo1调节的细胞内Ca在成骨和成肌过程中的作用验证为对抗机械相关疾病提供了一个可能的治疗靶点。