Page 37 - Physico-Chemical Niche Conditions for Bone Cells

crucial importance for the transport of nutrients and oxygen through facilitated diffusion, and the transduction of mechanical signals. In other words, not only mature osteocytes can be affected by many factors, but also the early osteocytes which are embedded in a collagen matrix which is not completely calcified and which are relatively close to the bone surface. Early osteocytes are in a less calcified surrounding and likely less affected by hypoxia as oxygen tension is likely higher, however, in case of severe exercise or high altitude these cells may also sense hypoxia. Like in virtually all tissue, muscle is also affected by hypoxia via the HIF-1 signalling pathway [75]. Prolonged hypoxia does not promote angiogenesis in muscle [75]. However, hypoxia affects intracellular calcium concentration, which modulates muscle cell proliferation [76].
Physical Niche Conditions of (Early)-Osteocytes and Myoblasts
Mechanopresentation implies the presentation of mechanical load cues to be sensed by bone or muscle cells. When mechanical stimuli are applied to the cell surface or microenvironment, one or more ligands anchored on the cell surface to support mechanical force upon its application are required for mechanopresentation. Insoluble ligands such as integrins, syndecans, and dystroglycans are prerequisite, since soluble ligands cannot present mechanical cues. Mechanoreception is the process of attachment of the mechanopresenting ligand with the cell surface receptor that is exerted by mechanical load. The cell surface receptor is termed a cell mechanoreceptor, since it represents a molecule that senses and receives the mechanical load signal. This response may cause conformational changes of the cell surface-binding site of the ligand and receptor to change the bond properties. Mechanotransmission is executed by the mechanotransmitter, e.g. receptor and ligand. The mechanical load signal is transduced from the ligand-receptor binding site to the inside of the cell. Remarkably, the spreading of the mechanical load signal is not only limited to the mechanical force, since it does not only induce conformational changes of molecular signaling mechanisms, but it is also part of the mechanotransmission process, albeit its stimulatory effect on mechanotransduction that suggests that the mechanical stimuli are translated into biochemical signals. However, a model of tensegrity-based signaling in cells has been postulated, that proposes that the cytoskeleton constitutes of a pre-stressed tensegrity structure allowing force transmission from the ECM onto the cytoskeleton and nucleus [77]. The forces exerted via the ECM cause the release of mRNA and ribosomes attached to the cytoskeleton, and nuclear deformation or conformational changes of chromatin that affects gene transcription [78].
Mechanotransduction is either a local cell mechanosensing process or a whole cell mechanosensing process. Normally, a region of the receptor or its linked subunit structure undergoes conformational changes in a cell in response to a mechanical force waveform,
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