Page 45 - Physico-Chemical Niche Conditions for Bone Cells

morphology on functional bone adaptation and the disturbed bone remodeling process at old age. In aging muscle, the MuSC ability to proliferate is reduced, and is accompanied by fibrosis which increases the stiffness of the niche [94]. This enhanced niche stiffness may alter gene expression, since the MuSCs will sense this increase in stiffness via traction forces. However, the fibrosis will also alter the external loads applied to the cells. The impact of aging-associated fibrosis as well as this impaired regenerative capacity of the MuSC in aging muscle needs further investigation.
Reciprocal communication between cell and microenvironment plays a crucial role in maintaining normal cell or tissue function. The conditions that block these feedback loops, either by influencing intracellular or extracellular physical force distribution, cellular mechanosensing, or signal transduction, can result in various clinical phenotypes [80]. In the past years, more and more evidence has been provided that fine-tuning the feedback between the cells and their physical microenvironment is crucial to the cell structure and function, ranging from adhesion, spreading, and viability, to differentiation and proliferation [80]. Interference with cellular and microenvironmental mechanotransduction processes may thus lead to diseases affecting various tissues and/or organs [80]. Studying the underlying mechanisms of these diseases may lead to adopt new therapeutic strategies, such as improvement of tissue engineering design and enhancement of biomaterials, and also provide us with more opportunities to learn, know, and understand physicochemical niche conditions, mechanosensing, and mechanobiology in normal cells and physiology [80].
CONCLUSIONS
Osteocyte and MuSC function is dependent on their native niche characteristics, but the cells also affect their own niche. It is a two-way street. The process of mechanotransduction can be divided into distinct stages. First, osteoblasts, osteocytes, or MuSCs subjected to PFF secrete signal molecules such as NO and prostaglandins. Second, integrins form clusters with intracellular anchoring complexes which relay signaling molecules into the cell from the ECM. Third, signaling molecules affect the arrangement or polymerization of actin and tubulin. Fourth, actin and tubulin connect the plasma membrane to the nucleus membrane, which might play a role in determining the cell and nucleus morphology and volume. Finally, changes in cell and nucleus morphology and volume cause up-regulation of gene and protein expression. In the future, it needs to be determined whether, and which changes in cell morphology drive osteogenic differentiation, as well as the underlying mechanism. A combination of in vivo and in vitro studies is necessary to determine the effects of physicochemical niche conditions on both bone and muscle cells, microenvironmental mechanosensing, and mechanotransduction. Targeting cell and microenvironment is
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