Page 18 - Physico-Chemical Niche Conditions for Bone Cells

General introduction
eukaryotic cells [49]. The internal mechanical signal (resulting from e.g. stretching of the cells) has been shown to drive fusion and fission through an elastocapillary instability [49,50]. Therefore, mechanical stimuli-induced changes of mitochondria might also play an important role in mechanosensing and mechanotransduction by bone cells. Considering the importance of integrins and the cytoskeleton for mechanotransduction, it will not come as a surprise that cell shape is also important for mechanosensing [51]. A flat cell has a stiffer cytoskeletal configuration compared with a round cell, and round cells seem to be much more mechanosensitive than flat cells [51].
Scope of the thesis
The main aim of the studies presented in this thesis was to investigate the effect of physical and (bio)chemical niche conditions on (pre)osteoblast mechanoresponse and behavior (Fig. 2). We have evaluated physical factors (pulsating fluid shear stress) and biochemical factors (RGD and supported lipid bilayers) as niche conditions that affect the pre-osteoblast response and behavior, i.e. cytoskeleton, cell body/nucleus shape, mitochondrial shape and structure, and cell differentiation. We have chosen to evaluate these particular parameters because they are closely interconnected and are involved in the transduction of both physical and (bio)chemical factors, leading to the changes in cell shape and function. In order to achieve our aim, we addressed the following specific objectives/scientific questions in this thesis:
1. How do physicochemical niche conditions affect the manner by which bone and muscle cells sense mechanical cues, thereby determining cell fate and function (Chapter 2)?
2. How are bone cell and nuclear morphological characteristics affected by physiological mechanical loading (Chapter 3)?
3. Is mechanical loading directly sensed by osteoblasts, e.g. through changes in shape, or does mechanical loading stimulate the production of osteoblast-stimulating factors? (Chapter 4)?
4. Does pulsating fluid flow affect bone cell mitochondrial network structure and dynamics (Chapter 5)?
5. Does arginine-glycine-aspartate-functionalized affect pre-osteoblast adhesion, morphology, proliferation, and osteogenic potential (Chapter 6)?
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