Hansda Surajit, Das Hiranmoy
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, ARB Suite 2116, 1406 South Coulter Street, Amarillo, TX 79106, USA.
Biology (Basel). 2025 Sep 17;14(9):1279. doi: 10.3390/biology14091279.
The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone-brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone-brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders.
骨骼和大脑虽然在结构和功能上截然不同，但在物理、分子和发育方面却有着显著的相似之处。新出现的证据表明，这些系统之间存在由激素、细胞因子、细胞外囊泡（EVs）和神经信号介导的动态双向串扰。骨源性因子，如骨钙素（OCN）、lipocalin-2和成纤维细胞生长因子（FGF）23，会影响认知功能、情绪和神经发生，而脑源性和神经源性介质，包括瘦素、血清素和交感神经信号，则会调节骨重塑。炎症和衰老会破坏这种交流，导致认知能力下降、骨质疏松症和其他与年龄相关的疾病。干细胞和细胞外囊泡也被认为是这一轴中的介质，为再生策略提供了思路。分子信号通路和转录调节因子，如Wnt/β-连环蛋白、瘦素、核因子κB受体激活剂配体（RANKL）、硬化蛋白（SOST）和核因子κB（NF-κB），在维持骨-脑稳态中起着关键作用。此外，神经退行性变和骨质流失之间共享的生物标志物和病理联系提示了新的诊断和治疗机会。研究支持这种器官间的交流，但仍需要进一步的机制和转化研究。本综述强调了骨-脑串扰的分子基础，重点关注炎症、衰老和调节途径，同时聚焦于生物标志物发现和治疗靶点的未来方向。了解这种串扰可能有助于骨和脑疾病的早期诊断和双靶点干预。
