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Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit.

Publication ,  Journal Article
Ryser, MD; Nigam, N; Komarova, SV
Published in: J Bone Miner Res
May 2009

During bone remodeling, bone-resorbing osteoclasts and bone-forming osteoblasts are organized in bone multicellular units (BMUs), which travel at a rate of 20-40 mum/d for 6-12 mo, maintaining a cylindrical structure. However, the interplay of local BMU geometry with biochemical regulation is poorly understood. We developed a mathematical model of BMU describing changes in time and space of the concentrations of proresorptive cytokine RANKL and its inhibitor osteoprotegerin (OPG), in osteoclast and osteoblast numbers, and in bone mass. We assumed that osteocytes surrounding a microfracture produce RANKL, which attracted osteoclasts. OPG and RANKL were produced by osteoblasts and diffused through bone, RANKL was eliminated by binding to OPG and RANK. Osteoblasts were coupled to osteoclasts through paracrine factors. The evolution of the BMU arising from this model was studied using numerical simulations. Our model recapitulated the spatio-temporal dynamics observed in vivo in a cross-section of bone. In response to a RANKL field, osteoclasts moved as a well-confined cutting cone. The coupling of osteoclasts to osteoblasts allowed for sufficient recruitment of osteoblasts to the resorbed surfaces. The RANKL field was the highest at the microfracture in front of the BMU, whereas the OPG field peaked at the back of the BMU, resulting in the formation of a RANKL/OPG gradient, which strongly affected the rate of BMU progression and its size. Thus, the spatial organization of a BMU provides important constraints on the roles of RANKL and OPG as well as possibly other regulators in determining the outcome of remodeling in the BMU.

Duke Scholars

Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

May 2009

Volume

24

Issue

5

Start / End Page

860 / 870

Location

England

Related Subject Headings

  • Time Factors
  • Solubility
  • RANK Ligand
  • Osteoprotegerin
  • Osteoblasts
  • Models, Biological
  • Fractures, Bone
  • Computer Simulation
  • Bone and Bones
  • Anatomy & Morphology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ryser, M. D., Nigam, N., & Komarova, S. V. (2009). Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit. J Bone Miner Res, 24(5), 860–870. https://doi.org/10.1359/jbmr.081229
Ryser, Marc D., Nilima Nigam, and Svetlana V. Komarova. “Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit.J Bone Miner Res 24, no. 5 (May 2009): 860–70. https://doi.org/10.1359/jbmr.081229.
Ryser MD, Nigam N, Komarova SV. Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit. J Bone Miner Res. 2009 May;24(5):860–70.
Ryser, Marc D., et al. “Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit.J Bone Miner Res, vol. 24, no. 5, May 2009, pp. 860–70. Pubmed, doi:10.1359/jbmr.081229.
Ryser MD, Nigam N, Komarova SV. Mathematical modeling of spatio-temporal dynamics of a single bone multicellular unit. J Bone Miner Res. 2009 May;24(5):860–870.
Journal cover image

Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

May 2009

Volume

24

Issue

5

Start / End Page

860 / 870

Location

England

Related Subject Headings

  • Time Factors
  • Solubility
  • RANK Ligand
  • Osteoprotegerin
  • Osteoblasts
  • Models, Biological
  • Fractures, Bone
  • Computer Simulation
  • Bone and Bones
  • Anatomy & Morphology