Allosteric control model of bone remodelling containing periodical modes.
To help to understand the modelling process that occurs when a scaffold is implanted it is vital to understand the rather complex bone remodelling process prevalent in native bone. We have formulated a mathematical model that predicts osteoactivity both in scaffolds, as well as in bone in vivo and could set a basis for the more detailed allosteric models. The model is extended towards a bio-cybernetic vision of basic multicellular unit (BMU) action, when some of the regulation loops have been modified to reflect the allosteric control mechanisms, developed by Michaels-Menten, Hill, Koshland-Nemethy-Filmer, Monod-Wyman-Changeux. By implementation of this approach a four-dimensional system was obtained that shows steady cyclic behaviour using a wide range of constants with clear biological meaning. We have observed that a local steady state appears as a limiting cycle in multi-dimensional phase space and this is discussed in this paper. Physiological interpretation of this limiting four-dimension cycle possibly related to a conservative-like value has been proposed. Analysis and simulation of the model has shown an analogy between this conservative value, as a kind of substrate-energy regenerative potential of the bone remodelling system with a molecular nature, and to the classical physical value--energy. This dynamic recovery potential is directed against both mechanical and biomechanical damage to the bone. Furthermore, the current model has credibility when compared to the normal bone remodelling process. In the framework of widely recognised Hill mechanisms of allosteric regulation the cyclic attractor, described formerly for a pure cellular model, prevails for different forms of feedback control. This result indicates the viability of the proposed existence of a conservative value (analogous to energy) that characterises the recovery potential of the bone remodelling cycle. Linear stability analysis has been performed in order to determine the robustness of the basic state, however, additional work is required to study a wider range of constants.
Moroz
Adam
A
Rapid Prototyping and Manufacturing group, Faculty of Computing Science and Engineering, De Montfort University, 49 Oxford Street, Leicester, LE1 5XY, UK. amoroz@dmu.ae.uk
Wimpenny
David Ian
DI
D000494:Allosteric Regulation; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003198:Computer Simulation; D005246:Feedback / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D010012:Osteogenesis / Q000502:physiology*; D010507:Periodicity