Guan Qiao, Cao Yanting, Zou Jun, Zhang Lingli
School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
College of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China.
Biology (Basel). 2025 Aug 22;14(9):1112. doi: 10.3390/biology14091112.
In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood-brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor κB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer's disease: reduced bone density exacerbates Alzheimer's disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities.
近年来，骨-脑轴的双向调节机制已成为跨学科研究的热点。在本文中，我们系统地综述了骨骼与中枢神经系统之间的解剖学和功能联系，重点关注骨源性信号对脑功能的调节及其临床转化潜力。在解剖学层面，血脑屏障的通透性机制和脑室周围器官的独特结构为骨-脑信息传递奠定了解剖学基础。创新性发现表明，骨细胞网络（骨髓间充质干细胞、成骨细胞、破骨细胞和骨髓单核细胞）通过分泌骨钙素、脂质转运蛋白2、核因子κB受体激活因子配体和成纤维细胞生长因子23等因子，以及外泌体介导的远程信号传导，直接调节神经可塑性和炎症微环境。临床研究揭示了骨质疏松症与阿尔茨海默病之间的双向恶性循环：骨密度降低通过血小板衍生生长因子BB等途径加剧阿尔茨海默病的病理过程，而与阿尔茨海默病相关的神经退行性变进一步加速骨质流失。突破在于发现抗骨质疏松药物（如双膦酸盐）可改善认知功能。相反，神经活性药物可调节骨代谢，为合并症的治疗提供了新策略。此外，全身振动疗法通过机械-破骨细胞信号轴调节骨-脑相互作用，显示出非药物干预的潜力。未来，整合多组生物标志物以开发早期诊断工具对于促进骨-脑合并症的精准预防和治疗至关重要。本文为神经骨骼合并症的机制和治疗策略提供了新的视角。
