Functional determinants of bone structure: Beyond Wolff's law of bone transformation
1992; Elsevier BV; Volume: 13; Issue: 6 Linguagem: Inglês
10.1016/8756-3282(92)90082-8
ISSN8756-3282
Autores Tópico(s)Cellular Mechanics and Interactions
ResumoFrost has suggested that functional loading controls bone mass and form as a thermostat controls temperature—by homeostatic regulation (i.e., by negative feedback). Yet, the literature contains many results that appear incompatible with the "mechanostat" hypothesis. We propose that a different type of regulation—epigenetic—is important in many aspects of bone adaptation. Epigenetic regulation, as we describe it, involves positive feedback loops and promotes differentiation as it forces elements of a system to choose between two extreme levels called attractors. Our review of bone adaptation data suggests that lamellar bone formation is regulated homeostatically, whereas the formation of woven-fibered bone or fracture callus is regulated epigenetically, that is, woven bone formation is brought about by a positive feedback loop that stimulates osteoblasts to a state of greater individual activity. This positive feedback loop may involve transforming growth factor β (TGFβ), for which autocrine induction has been demonstrated in vivo, as well as other factors, including insulin-like growth factor (IGF) and prostaglandin E2 (PGE2). The importance of this model is that it provides a mechanism for many unexplained nonlinear events that have been observed in bone adaptation experiments. Furthermore, it provides insights into the genesis of woven bone, which is a critical step in the process of bone healing and regeneration.
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