Department of Orthopedic Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi'an, China.
Exp Cell Res. 2024 Oct 1;442(2):114270. doi: 10.1016/j.yexcr.2024.114270. Epub 2024 Oct 9.
Weightlessness osteoporosis, which progresses continuously and has limited protective effects, has become one of the major problems that need to be solved in manned spaceflight. Our study aims to investigate the regulatory role of PHF8 in disuse osteoporosis by observing the expression of PHF8 in bone marrow mesenchymal stem cells (BMSCs) under simulated weightlessness conditions. Therefore, we used the model of ground-based microgravity simulated by disuse osteoporosis patients and tail suspension in mice to simulate microgravity in vivo, and measured the expression of PHF8 in bone tissue. Subsequently, we used the 2D gyroscope to simulate the weightless effect on bone marrow mesenchymal stem cells. In the weightless condition, we detected the proliferation, apoptosis, osteogenesis, and osteogenic differentiation functions of BMSCs. We also detected the expression of osteogenic-related transcription factors after knocking down and overexpressing PHF8. Our results show that the weightless effect can inhibit the proliferation, osteogenesis, and osteogenic differentiation functions of BMSCs, while enhancing their apoptosis; and overexpression of PHF8 can partially alleviate the osteoporosis caused by simulated weightlessness, providing new ideas and clues for potential drug targets to prevent weightlessness and disuse osteoporosis.
失重性骨质疏松症持续进展且防护效果有限，已成为载人航天需要解决的主要问题之一。本研究旨在通过观察模拟失重条件下骨髓间充质干细胞（BMSCs）中 PHF8 的表达，探讨 PHF8 在废用性骨质疏松症中的调控作用。因此，我们使用由骨质疏松症患者和小鼠尾部悬吊引起的地面模拟微重力模型来模拟体内微重力，并测量骨组织中 PHF8 的表达。随后，我们使用二维转椅模拟对骨髓间充质干细胞的失重效应。在失重条件下，我们检测了 BMSCs 的增殖、凋亡、成骨和向成骨分化功能。我们还检测了敲低和过表达 PHF8 后成骨相关转录因子的表达。我们的结果表明，失重效应可抑制 BMSCs 的增殖、成骨和向成骨分化功能，同时增强其凋亡；过表达 PHF8 可部分缓解模拟失重引起的骨质疏松症，为预防失重和废用性骨质疏松症的潜在药物靶点提供了新的思路和线索。
