Mechanical Stimulation Drives Multicellular Synergy and Signaling Pathways in Developing Skeletal Tissues

The growth period represents a crucial bone mass acquisition and skeletal development phase. During this stage, bone tissues exhibit remarkable resilience and high plasticity, thereby 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. Therefore, exploring how exercise and mechanical stimuli influence bone development during this critical period and their underlying mechanisms is essential. This study provides a comprehensive review of the effects of exercise and mechanical stimulation on bone development and growth during the growth period. In particular, it focuses on the state of bone cells, such as bone marrow mesenchymal stem cells, osteoblasts, chondrocytes, osteoclasts, and osteocytes, and the molecular mechanisms governing mechanoregulation. Additionally, this study delves into the signaling pathways influenced by exercise and mechanical stimuli, including Wnt/β-catenin, bone morphogenetic protein/SMAD proteins, phosphatidylinositol 3-kinase/protein kinase, receptor activator of nuclear factor κB-receptor activator of nuclear factor κB ligand-osteoprotegerin, and mitogen-activated protein kinase. These pathways are pivotal in regulating bone formation, resorption, and remodeling. This study also analyzes the impact of exercise-modulated signaling pathways on bone development in children and adolescents to provide theoretical insights and practical guidance for designing scientifically sound exercise programs. Ultimately, these findings contribute to optimizing bone health strategies during youth, maintaining long-term bone health, and reducing the risk of bone-related disorders later in life.