Page 28 - Physico-Chemical Niche Conditions for Bone Cells

Physicochemical niche conditions and mechanosensing
on how these cellular processes are affected by ageing and disease. For a better overall understanding of mechanotransduction by musculo-skeletal-derived cells in disease and ageing, more studies should focus on fundamental cellular responses to mechanical perturbations of musculo-skeletal-derived cells in isolation, but also in relation to the environment in which the mechanosensitive cell types reside.
Mechanical loading of bone and muscle causes cellular, cytoskeletal, and nuclear deformation [14], and stimulates transmembrane molecules acting as mechanosensors [12,15]. The transmembrane molecules available to function for a given cell depend on the immediate environment of said cell, i.e. the presence of different types of neighboring cells contacting the mechanosensitive cell and the composition of the extracellular matrix (ECM). In addition, the availability of oxygen, signaling molecules, and physical properties of the ECM, are all likely to affect the ability of musculo-skeletal-derived cells to sense and respond to mechanical cues. These far-reaching consequences of the exact chemical, physical, and cellular composition of the direct environment in which a specific cell type resides for the ability of said cell type to function, has been widely accepted in the field of stem cell research, where it is known as “niche condition”. This review provides a literature-based overview of the physicochemical niche conditions of (pre)-osteocytes and myocytes and how these niche conditions affect the manner in which mechanical cues are sensed, thereby determining cell fate and function. We focus on (pre)-osteocytes since these are the most frequently studied cells in relation to mechanosensing, and seem to be ideally situated in an environment that allows amplification of mechanical signals. In addition, osteocytes are extremely potent producers of paracrine and endocrine signaling molecules, making them orchestrators of bone mass and bone architecture [16]. For muscle, we focus on the muscle stem cell (MuSC), also referred as satellite cell, as this is the mono-nuclear muscle precursor cell, required for myofiber regeneration and myonuclear accretion in the host myofiber.
Different Niche Types in Bone and Muscle
Multiple subtypes of stem cell niches have been distinguished, i.e. simple niches, complex niches, and storage niches [17]. The “simple niche” includes one type of cell interacting with another via cadherins, ephrins, connexins, and other cell-cell molecules [18,19]. The network of interconnected mature osteocytes within a single osteon could be considered a simple niche. The “complex niche” includes different cell types that coordinately regulate each other to develop multiple cell behavior by means of niche regulatory signals [17]. In bone, the niche comprised of (early)-osteocytes, osteoclasts, osteoblasts and their respective stem cells are a perfect example of a “complex niche”. Precise regulation of bone mass, and specifically bone architecture, requires complex interaction between these cells [20]. The “storage niche” includes cells that are maintained in the niche and quiescent until activated by external
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