Yin Jiahao, Guan Qiao, Chen Minyou, Cao Yanting, Zou Jun, Zhang Lingli
College of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China.
School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
Int J Mol Sci. 2025 Apr 9;26(8):3501. doi: 10.3390/ijms26083501.
Research findings reveal that thermal environments precisely regulate the skeletal system through a triple regulation of "structural morphology-cellular dynamics-molecular mechanisms": At the tissue morphology level, moderate heat exposure can promote increased bone density and longitudinal growth, as well as improved fracture load and yield point, but may negatively affect geometric shape and cortical bone thickness. Continuous high-temperature exposure harms bone structure, manifested as changes in biomechanical characteristics such as decreased toughness and rigidity. At the cellular level, thermal environments directly affect the proliferation/apoptosis balance of osteoblasts and osteoclasts, and by regulating osteocyte network activity and bone marrow mesenchymal stem cell fate decisions, these four cell populations form temperature-dependent metabolic regulatory circuits. At the molecular dimension, heat stress can activate the release of neural factors such as CGRP and NPY, which possess dual regulatory functions promoting both bone formation and resorption; simultaneously achieving coordinated regulation of angiogenesis and fat inhibition through VEGF and TGFβ. The thermal environment-bone regulatory mechanisms revealed in this study have important translational value: they not only provide theoretical basis for biomechanical protection strategies for high-temperature workers and athletes, but also offer innovative entry points for analyzing the pathological mechanisms of heat stroke secondary bone injury and osteoporosis through heat stress-related signaling pathways, while establishing a theoretical foundation for the development of temperature-responsive functionalized biomaterials in bone tissue engineering.
研究结果表明，热环境通过“结构形态-细胞动力学-分子机制”的三重调节精确调控骨骼系统：在组织形态学层面，适度热暴露可促进骨密度增加和纵向生长，以及改善骨折负荷和屈服点，但可能对几何形状和皮质骨厚度产生负面影响。持续高温暴露会损害骨骼结构，表现为生物力学特性的改变，如韧性和刚性降低。在细胞层面，热环境直接影响成骨细胞和破骨细胞的增殖/凋亡平衡，并且通过调节骨细胞网络活性和骨髓间充质干细胞的命运决定，这四种细胞群体形成温度依赖性代谢调节回路。在分子维度，热应激可激活神经因子如降钙素基因相关肽（CGRP）和神经肽Y（NPY）的释放，它们具有促进骨形成和吸收的双重调节功能；同时通过血管内皮生长因子（VEGF）和转化生长因子β（TGFβ）实现血管生成和脂肪抑制的协同调节。本研究揭示的热环境-骨骼调节机制具有重要的转化价值：它们不仅为高温工作者和运动员的生物力学保护策略提供理论依据，而且为通过热应激相关信号通路分析中暑继发骨损伤和骨质疏松症的病理机制提供创新切入点，同时为骨组织工程中温度响应功能化生物材料的开发奠定理论基础。
