Interoceptive regulation of skeletal tissue homeostasis and repair

Abstract

Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

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Funding

This work was supported by the National Natural Science Foundation of China (No.82172408, 81772314, and 81922045); Original Exploration project (22ZR1480300) and Outstanding Academic Leaders (Youth) project (21XD1422900) of Shanghai Science and Technology Innovation Action Plan; Principle Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University Medical College “Two-hundred Talent” Program (No.20191829); The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang (No.SHDC2020CR4032); Shanghai Excellent Academic Leader Program; and Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration (No.20DZ2254100).

National Natural Science Foundation of China (No.81902234)