A theoretical model for simulating effect of parathyroid hormone on bone metabolism at cellular level.
A mathematical model is developed for simulating anabolic behaviour of bone affected by Parathyroid Hormone (PTH) in this paper. The model incorporates a new understanding on the interaction of PTH and other factors with the RANK-RANKL-OPG pathway into bone remodelling, which is able to simulate anabolic actions of bone induced by PTH at cellular level. The RANK-RANKL-OPG pathway together with the dual action of TGF-beta, which represent the core of coupling behaviour between osteoblasts and osteoclasts which are two cell types specialising in the maintenance of bone integrity, are widely considered essential for the regulation of bone remodelling at cellular level. Moreover, the anabolic effect of PTH on bone remodelling (mainly causing bone gain) is significant for therapies of bone disease such as osteoporosis. Although the Food and Drug Administration of United States has approved PTH as an anabolic treatment for osteoporosis, the corresponding underlying mechanism of bone anabolism remains elusive. The proposed mathematical model provides a detailed biological description of bone remodelling using the latest experimental findings and can explain the mechanism of bone anabolic action by PTH that is administered intermittently as well as catabolic effect when applied continuously. The development of such a model provides a rational basis for developing more biologically extensive models that may support the design of optimal dosing strategies for different therapies such as PTH-based anti-osteoporosis treatments.
Wang
Yanan
Y
Department of Engineering, Australian National University, Canberra, ACT 0200, Australia.
Qin
Qing-Hua
QH
Kalyanasundaram
Shankar
S
D000465:Algorithms; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003198:Computer Simulation; D004334:Drug Administration Schedule; D006801:Humans; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016212:Transforming Growth Factor beta