In vivo models of muscle stimulation and mechanical loading in bone mechanobiology

Mechanical biology and biomechanical signal transduction is a novel approach to attenuate musculoskeletal degeneration, and the understanding of specific cellular responses is critical to delineate the underlying mechanism. Dynamic mechanical signals with optimized loading signals, i.e., intensity and frequency, have been shown to have the potential to regulate bone and cartilage adaptation. Mechanotransduction pathways are of great interest in elucidating how mechanical signals produce such observed effects, including reduced bone loss, increased bone formation, and osteogenic cell differentiation. The objective of this chapter is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology. In this chapter, we discuss the potential for mechanical loading to induce dynamic bone fluid flow, i.e., generated by the intramedullary pressure and strains in bone; regulation of bone adaptation; and optimization of stimulation parameters in the loading regimen. The potential for mechanical loading to regulate bone fluid flow and microcirculation is also discussed. Particular attention is allotted to the responses of mechanical loading, including potential cellular and molecular pathways, osteocytes associated with Wnt signaling, the elevation of marrow stem cells and suppression of adiposis cells, and the roles of LRP5 and microRNA. Altogether, these discussed data highlight the complex yet highly coordinated process of mechanotransduction in bone tissue regeneration.