Primary cilia as mechanosensors in musculoskeletal homeostasis and disease
Huibo Ti, Zhenyu Zhang, Xielin Yan, Hailin Hu, Keyue Zhang, Shuwen Shi, Jun‐Jie Wu, Hao Nie, Zheng‐Dong Yuan, Yuechun Chen, Yifei Fu, Ming-Dong Zhao, Feng‐Lai Yuan, Xia Li
Abstract
The musculoskeletal system relies on precise mechanical signal transduction to maintain physiological homeostasis, yet the underlying mechanisms remain incompletely characterized. Primary cilia (PC), membrane-bound organelles that protrude into the extracellular matrix, acting as cellular sensors to integrate biomechanical forces into cellular responses. Moreover, their dynamic assembly and disassembly are tightly coupled to mechanical stress perception, which also suggests a pivotal role in regulating musculoskeletal tissue function. This review systematically synthesizes current evidence on PC-mediated mechanical signaling pathways in bone, muscle, cartilage health, intervertebral disc homeostasis, and tendon matrix crosslinking, elucidating how these structures influence tissue maintenance and repair. We explore the dynamic assembly and disassembly of PC in response to mechanical forces and their impact on downstream signaling pathways. We explore the assembly and disassembly process of PC in response to mechanical forces and their impact on downstream signaling pathways. By identifying key regulatory targets, we discuss the potential regulatory targets of PC for therapeutic interventions in musculoskeletal disorders, offering new perspectives for disease management in the future.