Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological–mechanical therapies to treat bone loss diseases such as osteoporosis.

[1]  Alexander G Robling,et al.  Improved Bone Structure and Strength After Long‐Term Mechanical Loading Is Greatest if Loading Is Separated Into Short Bouts , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  M. K. Knothe Tate,et al.  The osteocyte. , 2004, The international journal of biochemistry & cell biology.

[3]  Cheryl L. Ackert-Bicknell,et al.  Nitric Oxide Regulates Receptor Activator of Nuclear Factor-κB Ligand and Osteoprotegerin Expression in Bone Marrow Stromal Cells , 2004 .

[4]  J. Klein-Nulend,et al.  MECHANOTRANSDUCTION IN BONE : ROLE OF THE LACUNOCANALICULAR NETWORK , 1999 .

[5]  R Ronald Ruimerman,et al.  Modeling and remodeling in bone tissue , 2005 .

[6]  Rik Huiskes,et al.  Effects of mechanical forces on maintenance and adaptation of form in trabecular bone , 2000, Nature.

[7]  Ching‐Jen Wang,et al.  Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis inhibitory activity in bone marrow stromal cells from ovariectomized rats. , 2004, Endocrinology.

[8]  R Huiskes,et al.  A theoretical framework for strain-related trabecular bone maintenance and adaptation. , 2005, Journal of biomechanics.

[9]  Theo H Smit,et al.  Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon--a proposal. , 2003, Journal of biomechanics.

[10]  M. Mullender,et al.  Mechanotransduction of bone cellsin vitro: Mechanobiology of bone tissue , 2006, Medical and Biological Engineering and Computing.

[11]  Theo H Smit,et al.  Nitric oxide production by bone cells is fluid shear stress rate dependent. , 2004, Biochemical and biophysical research communications.

[12]  C. Rubin,et al.  Anabolism: Low mechanical signals strengthen long bones , 2001, Nature.

[13]  Geoff Smith,et al.  Phenomenological model of bone remodeling cycle containing osteocyte regulation loop. , 2006, Bio Systems.

[14]  E H Burger,et al.  Mechanotransduction in bone cells proceeds via activation of COX-2, but not COX-1. , 2003, Biochemical and biophysical research communications.

[15]  E H Burger,et al.  Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes--a cytoskeleton-dependent process. , 1996, Biochemical and biophysical research communications.

[16]  P. Nijweide,et al.  Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes. , 1999, The American journal of physiology.

[17]  S. Keila,et al.  Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro. , 2001, The Journal of endocrinology.

[18]  P. Niederer,et al.  In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. , 2000, The Journal of experimental biology.

[19]  Peter Pivonka,et al.  Model structure and control of bone remodeling: a theoretical study. , 2008, Bone.

[20]  I. Heyligers,et al.  Estrogen enhances mechanical stress-induced prostaglandin production by bone cells from elderly women. , 2001, American journal of physiology. Endocrinology and metabolism.

[21]  H Weinans,et al.  A physiological approach to the simulation of bone remodeling as a self-organizational control process. , 1994, Journal of biomechanics.

[22]  S. Cowin,et al.  A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. , 1994, Journal of biomechanics.

[23]  S. Wimalawansa,et al.  Nitric oxide and bone , 2010, Annals of the New York Academy of Sciences.

[24]  T J Chambers,et al.  The role of prostaglandins and nitric oxide in the response of bone to mechanical forces. , 1999, Osteoarthritis and cartilage.

[25]  H. Grootenboer,et al.  The behavior of adaptive bone-remodeling simulation models. , 1992, Journal of biomechanics.

[26]  C. Leu,et al.  Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2). , 2001, Molecular pharmacology.

[27]  Li Shi,et al.  A mathematical model for simulating the bone remodeling process under mechanical stimulus. , 2007, Dental materials : official publication of the Academy of Dental Materials.

[28]  Alexander G Robling,et al.  Biomechanical and molecular regulation of bone remodeling. , 2006, Annual review of biomedical engineering.

[29]  A. Parfitt Osteonal and hemi‐osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone , 1994, Journal of cellular biochemistry.

[30]  M G Mullender,et al.  Mechanobiology of bone tissue. , 2005, Pathologie-biologie.

[31]  L. Raisz Physiology and pathophysiology of bone remodeling. , 1999, Clinical chemistry.

[32]  Hwj Rik Huiskes,et al.  A Computer-simulation Model Relating Bone-cell Metabolism to Mechanical Adaptation of Trabecular Architecture , 2001 .

[33]  J. A. Baart,et al.  Donor Age and Mechanosensitivity of Human Bone Cells , 2002, Osteoporosis International.