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BIOMD0000000148 - Komarova2003_BoneRemodeling


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Reference Publication
Publication ID: 14499354
Komarova SV, Smith RJ, Dixon SJ, Sims SM, Wahl LM.
Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling.
Bone 2003 Aug; 33(2): 206-215
CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.  [more]
Original Model: BIOMD0000000148.origin
Submitter: Harish Dharuri
Submission ID: MODEL6029826395
Submission Date: 06 Sep 2007 09:06:51 UTC
Last Modification Date: 09 Oct 2014 17:24:13 UTC
Creation Date: 30 Jul 2007 21:56:00 UTC
Encoders:  Harish Dharuri
set #1
bqbiol:hasProperty Human Disease Ontology Paget's disease of bone
Human Disease Ontology osteoarthritis
Human Disease Ontology osteoporosis
set #2
bqbiol:isVersionOf Gene Ontology regulation of bone remodeling
set #3
bqbiol:occursIn Taxonomy Chordata

This a model from the article:
Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling.
Komarova SV, Smith RJ, Dixon SJ, Sims SM, Wahl LM Bone2003 Aug;33(2):206-15 14499354,
Bone remodeling occurs asynchronously at multiple sites in the adult skeleton and involves resorption by osteoclasts, followed by formation of new bone by osteoblasts. Disruptions in bone remodeling contribute to the pathogenesis of disorderssuch as osteoporosis, osteoarthritis, and Paget's disease. Interactions among cells of osteoblast and osteoclast lineages are critical in the regulation of bone remodeling. We constructed a mathematical model of autocrine and paracrine interactions among osteoblasts and osteoclasts that allowed us to calculate cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Themodel predicted different modes of dynamic behavior: a single remodeling cycle in response to an external stimulus, a series of internally regulated cycles of bone remodeling, or unstable behavior similar to pathological bone remodeling in Paget's disease. Parametric analysis demonstrated that the mode of dynamic behaviorin the system depends strongly on the regulation of osteoclasts by autocrine factors, such as transforming growth factor beta. Moreover, simulations demonstratedthat nonlinear dynamics of the system may explain the differing effects of immunosuppressants on bone remodeling in vitro and in vivo. In conclusion, the mathematical model revealed that interactions among osteoblasts and osteoclasts result in complex, nonlinear system behavior, which cannot be deduced from studies of each cell type alone. The model will be useful in future studies assessing the impact of cytokines, growth factors, and potential therapies on the overall process ofremodeling in normal bone and in pathological conditions such as osteoporosis and Paget's disease.

The model reproduces Fig 2A and Fig 2B of the paper. Note that the Y-axis scale is not right, the osteoblast steadystate is approximatley 212 and not 0 as depicted in the figure. Also, there is atypo in the equation for x2_bar which has been corrected here. Model successfully tested on MathSBML.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Publication ID: 14499354 Submission Date: 06 Sep 2007 09:06:51 UTC Last Modification Date: 09 Oct 2014 17:24:13 UTC Creation Date: 30 Jul 2007 21:56:00 UTC
Mathematical expressions
Osteoclast production Osteoclast removal Osteoblast production Osteoblast removal
Bone resorption Bone formation    
Assignment Rule (variable: gamma) Assignment Rule (variable: Steady state osteoclast) Assignment Rule (variable: Steady state osteoblast)  
event_0000001 event_0000003 event_0000002 event_0000004
Physical entities
Compartments Species
compartment Osteoclast Osteoblast Steady state osteoclast
Steady state osteoblast Bone mass Cells actively resorbing bone
Cells actively forming bone    
Global parameters
alpha1 alpha2 beta1 beta2
g11 g21 g12 g22
k1 k2 gamma flag_resorption
Reactions (6)
 Osteoclast production  ↔ [Osteoclast];   {Osteoblast}
 Osteoclast removal [Osteoclast] ↔ ;  
 Osteoblast production  ↔ [Osteoblast];   {Osteoclast}
 Osteoblast removal [Osteoblast] ↔ ;  
 Bone resorption [Bone mass] ↔ ;   {Osteoclast} , {Steady state osteoclast}
 Bone formation  ↔ [Bone mass];   {Osteoblast} , {Steady state osteoblast}
Rules (3)
 Assignment Rule (name: gamma) gamma = g12*g21-(1-g11)*(1-g22)
 Assignment Rule (name: x1_bar) Steady state osteoclast = (beta1/alpha1)^((1-g22)/gamma)*(beta2/alpha2)^(g21/gamma)
 Assignment Rule (name: x2_bar) Steady state osteoblast = (beta1/alpha1)^(g12/gamma)*(beta2/alpha2)^((1-g11)/gamma)
Events (4)
flag_resorption = 1
flag_resorption = 0
flag_formation = 1
flag_formation = 0
   Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: compartment
Initial amount: 11.0
Compartment: compartment
Initial amount: 212.0
   Steady state osteoclast
Compartment: compartment
Initial amount: 0.0
   Steady state osteoblast
Compartment: compartment
Initial amount: 0.0
   Bone mass
Compartment: compartment
Initial amount: 100.0
   Cells actively resorbing bone
Compartment: compartment
Initial amount: 0.0
   Cells actively forming bone
Compartment: compartment
Initial amount: 0.0
Global Parameters (13)
Value: 3.0
Value: 4.0
Value: 0.2
Value: 0.02
Value: 0.5
Value: -0.5
Value: 1.0
Value: 0.24
Value: 0.0017
Representative curation result(s)
Representative curation result(s) of BIOMD0000000148

Curator's comment: (updated: 27 Aug 2009 14:48:21 GMT)

The figure corresponds to Figure 2A and 2B of the reference publication. The model was integrated and simulated using Mathematica 6.0 - MathSBML 2.7.1.