| Bone adapts readily and rapidly to its mechanical loading environment to give rise to a functionally well designed tissue and organ. The “mechanosensor” for bone adaptation is widely believed to be the osteocyte. However, to date we have only a very preliminary knowledge of how these cells function in this regard. Nevertheless, there is an emerging consensus that strain-induced fluid flow plays a key role in this mechanical signaling. If this is the case, the next key question in understanding osteocyte mechanosensory function then is: How do osteocytes detect this fluid flow? This background is described in Chapter 1.; In Chapter 2, based on fundamental assumptions about the pericellular matrix, its attachment to the cell process and cytoskeletal coupling, we propose a new hypothesis and mathematical model that makes the remarkable prediction that very small strains in live bone created by normal physical activity can be amplified 100-fold at the cellular level. Specifically, the new strain amplification hypothesis proposes that there are transverse filaments in the pericellular matrix surrounding the cell processes which tether the process to the canalicular wall and also adhesion proteins associated with the cell membrane that link these filaments to the intracellular actin cytoskeleton (IAC). According to this hypothesis, deformation of the IAC due to mechanical loading is caused by bone interstitial fluid flow creating a fluid drag on the transverse tethering filaments which in turn creates a tensile force or hoop tension in the IAC.; In Chapter 3 we describe experiments that confirm and quantify the essential biological elements assumed by this new model using several EM staining techniques. Measurements of the dimensions of osteocytic process and pericellular matrix structure were also performed to provide realistic values for the input parameters that were used in our theoretical model.; Chapter 4 summarizes the important new insights and suggests directions for future research. |
