Feasible Simulation of Diseases Related to Bone Remodelling and of Their Treatment

Abstract

A great advance in understanding mechanosensing and mechanotransduction of bone tissue has occurred in the past years. However, a clear answer is yet to come. There is plentiful evidence that most cells in human body are able to sense their mechanical environment, including osteoblasts and osteocytes. Li et al. found that marrow stromal cells change their proliferation rate and gene expression patterns in response to mechanical stimulation (Li et al, 2004). Ehrlich and Lanyon mention that osteocytes produce significantly higher levels of PGE2 (prostaglandin E2) and PGI2 (prostacylin) than osteoblasts and in vivo inhibition of prostaglandins prevents bone adaptation in response to mechanical strains (Ehrlich and Lanyon, 2002). Further, nitric oxide NO is also a mediator of mechanically induced bone formation. It is released, similarly, as prostanoids, in higher levels after exposure to physiological levels of mechanical loading. Moreover, Rubin discovered that dynamic loading down-regulates osteoclastic formation (Rubin et al, 2000) (more precisely, the strained bone cell downregulates its expression of RANKL (Rubin et al, 2004)), which suggests that mechanical forces play an important role in bone adaptation process. Candidate mechanoreceptors within a cell are stretch-activated channels, integrins (membrane spanning proteins that couple the cell to its extracellular environment), connexins (membrane spanning proteins that form channels that allow the direct exchange of small molecules with adjacent cells including intercellular communication via gap junctions), and membrane structure (Rubin, 2006). Nowadays, there is also a completely different possible explanation for transformation mechanical signal into a biochemical function. Valle et al. explain in their review that only a proper mechanical loading may lead to exposure of binding sites and thus enabling further biochemical processes to proceed (Valle, 2007). Most probably multiple mechanosensors are involved in receiving mechanical signals. Moreover, there are other studies showing the importance of many other mechanisms beside those mentioned above (Lemaire et al, 2004). On tissue level, it is clear that mechanical loading is important in the bone remodelling process. Heřt described an interaction between the mechanical stimulation of local cells and the bone adaptation process in the 1970s (Heřt et al, 1972), Frost observed the same behaviour in his clinical praxis and summed it up in his „Utah paradigm“ (Frost, 2004). More recently, the fundamental importance of dynamic loading was accepted. Comparison of the static versus the dynamic loading effects on bone remodelling is given in a nice and