Mechanoregulation of Developing Skeletal Tissues: Cellular and Molecular Responses to Mechanical Stimulation

Background: The growth period represents a crucial phase for bone mass acquisition and skeletal development, during which bone tissues exhibit remarkable resilience and high plasticity, laying a robust foundation for optimal bone strength. Growing bones are highly responsive to external stimuli, particularly exercise and mechanical loading. Appropriate physical activity or mechanical stimulation facilitates the attainment of peak bone mass and offers long-term protection against bone diseases. Understanding how exercise and mechanical stimuli influence bone development during this critical period and their underlying mechanisms is therefore essential for optimizing skeletal health outcomes. Methods: This comprehensive review synthesizes evidence from cellular and molecular biology, biomechanics, and exercise science to examine the effects of exercise and mechanical stimulation on bone development during the growth period. The review focuses on the state of bone cells including bone marrow mesenchymal stem cells, osteoblasts, chondrocytes, osteoclasts, and osteocytes, and explores the molecular mechanisms governing mechanoregulation. Key signaling pathways influenced by mechanical stimuli were systematically analyzed. Results: Mechanical stimulation drives multicellular synergy within developing skeletal tissues through complex signaling cascades. Key pathways regulated by exercise and mechanical stimuli include Wnt/β-catenin, bone morphogenetic protein/SMAD proteins, phosphatidylinositol ۳-kinase/protein kinase, receptor activator of nuclear factor κB-receptor activator of nuclear factor κB ligand-osteoprotegerin, and mitogen-activated protein kinase. These pathways play pivotal roles in regulating bone formation, resorption, and remodeling processes. The synergistic interactions among bone cell populations coordinate adaptive responses to mechanical loading, promoting optimal skeletal development. Exercise-modulated signaling pathways have significant impacts on bone development in children and adolescents, with appropriate mechanical stimulation enhancing osteoblast activity and bone formation while modulating resorptive processes. Conclusion: Understanding the mechanoregulatory mechanisms underlying skeletal development provides theoretical insights and practical guidance for designing scientifically sound exercise programs for youth. These findings contribute to optimizing bone health strategies during childhood and adolescence, supporting long-term skeletal integrity and reducing the risk of bone-related disorders later in life. Future research should explore the optimal timing, intensity, and duration of mechanical loading for maximizing skeletal benefits.

کلیدواژه ها:

Mechanical stimulation ، Bone development ، Signaling pathways ، Exercise ، Skeletal tissue ، Osteogenesis