Page 14 - Physico-Chemical Niche Conditions for Bone Cells

General introduction
lineage commitment of mesenchymal stem cells (MSCs) [26]. Soft matrices with an elastic modulus of 0.1-1 kPa specify MSCs to commit to a neurogenic phenotype, while stiffer matrices with an elastic modulus of 8-17 kPa induce MSCs to commit to a muscle phenotype, and stiff matrices with an elastic modulus of 25-40 kPa are osteogenic for MSCs [26]. Thus, matrix topography and stiffness, as physical factors for bone cells, play an important role in MSC lineage commitment and bone responses [25,27].
Biochemical micro-environment (niche) of bone
The biochemical micro-environment (niche) of bone is a complex milieu, including growth factors and cytokines, as well as collagen and other extracellular matrix proteins, enzymes, ions, and minerals, which are involved in the processes of bone formation, repair and remodeling [28]. All these (bio)chemical substances or processes can affect cell function (e.g. proliferation, differentiation) and bone remodeling in an autocrine, paracrine, or endocrine fashion [29]. In addition, bone cells are surrounded by bone matrix (osteocytes) or in close contact with bone matrix (osteoblasts), which contains collagen (mostly collagen type I), laminins (e.g. laminin-332), fibronectin, proteoglycans, and growth factors in bone [29,30]. Within the biochemical micro-environment (niche) of bone, the extracellular matrix contains proteins such as osteopontin, fibrinogen, vitronectin, and fibronectin [31]. Vitronectin and fibronectin are the primary glycoproteins to promote bone cell adhesion. It is worth noting that arginine-glycine-aspartic acid (RGD) existing in fibronectin guides bone cell adhesion as a primary cell attachment cue [32].
The biochemical environment affects matrix mineral nucleation, cell migration, adhesion, proliferation, differentiation, and death, resulting in bone growth and remodeling [28]. Bone, as a mineralized tissue, contains high amounts of calcium and phosphate, but also other ions. Osteoblasts are sensitive to this (bio)chemical micro-environment, and control the concentration of those minerals and other ions in the bone matrix [33]. Hydroxyapatite makes up bone mineral consisting of crystalline calcium phosphate. Hydroxyapatite formation occurs initially in association with both collagen and extracellular membrane-bound bodies known as matrix vesicles. Generally, this process determines the amount of calcium stored within bone [28,33].
Effect of biochemical factors on bone cell behavior
The (bio)chemical factors of bone permit and facilitate cell functions which result in matrix production and ossification. This environment is a dynamic and active (bio)chemical system which can transmit regulatory cues to the cells, leading to changes of cell morphology and gene expression, as well as nucleation, mineralization, and growth factors [29,34]. The (bio)chemical environment not only affects matrix production, but also influences cell adhesion,
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