Page 165 - Physico-Chemical Niche Conditions for Bone Cells
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these effects relate to changes in the actin cytoskeleton and focal adhesion formation
(Chapter 3).
3. To investigate whether osteoblasts produce a mix of signaling factors in the intermediate-
term after a physical stimulus (hours; physical niche) that affect osteogenic differentiation
of their neighboring osteoblasts in the long-term (days; biochemical niche) (Chapter 4).
4. To determine the effects of pulsating fluid flow (physical niche) on bone cell mitochondrial network structure and dynamics, as well as on the interaction between mitochondria and
actin filaments (Chapter 5).
5. To investigate adhesion, focal adhesion formation, morphology, proliferation, and
osteogenic potential of pre-osteoblasts cultured on RGD-functionalized supported lipid bilayers (SLBs) compared to unfunctionalized SLBs and poly-L-lysine (chemical niche; Chapter 6).
The cell environment (niche) is a 3D structure consisting of signaling molecules, extracellular matrix (ECM), and/or other cells [12,13]. Bone as well as muscle cells are subjected to mechanical loading resulting in changes in cell body and nucleus [14,15]. In these processes, many (bio)chemical factors and signaling molecules are involved. The latter may cause changes in cell function [16]. Therefore, a better understanding of the role of the cell environment (niche) in cell behavior is very important. In chapter 2, we introduced the concept of niches in bone and muscle. Physical niche conditions are applied to the cell or cell environment. A series of biochemical reactions occur in cells and their surrounding environment, including mechanosensing, mechanopresentation, and mechanotransduction [17]. The physical signal is exerted via the ECM, resulting in a modulation of cell body and nucleus, including conformational changes of chromatin [18]. The (bio)chemical niche conditions are the non-cell-bond (bio)chemical cues which are consistently available in the ECM environment and may change the cell biological response and function, including epitopes (e.g. integrins), soluble factors (growth factors, cytokines), small molecules (NO, prostaglandins, oxygen (O2)), and calcium (Ca2+) [17]. In addition, the subcellular niche is also important for mechanotransduction, e.g. the glycocalyx. When the glycocalyx is removed, the mechanical loading-induced NO production decreases [19]. A disturbance of the mechanotransduction process between cells and their surrounding environment may cause diseases influencing various tissues or organs [20]. A better understanding of the physical and (bio)chemical environment and mechanobiology at the cellular or subcellular levels might provide new opportunities for developing these new therapeutic strategies [20]. Based on the importance of physical and (bio)chemical niche conditions, in this thesis, pulsating fluid flow (PFF; physical niche condition) and RGD (biochemical niche condition) were tested for their effect on osteoblast morphology and function.
Chapter 7
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