metaid_0000035
event assignment: 251462
trigger: 251450
use values from trigger time: true
type: Event

metaid_0000014
constant: true
value: 1.0
type: Parameter

metaid_0000031
kinetic law: 251364
modifier: 251352
modifier: 251340
product: 251327
is version of: GO:0001503
fast: false
reversible: true
name: Bone formation
type: Reaction

metaid_0000004
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 11.0
in compartment: metaid_0000003
name: Osteoclast
type: Species

metaid_0000011
constant: true
value: 0.02
type: Parameter

metaid_0000028
kinetic law: 251314
modifier: 251301
modifier: 251288
reactant: 251275
is: GO:0045453
fast: false
reversible: true
name: Bone resorption
type: Reaction

metaid_0000024
kinetic law: 251196
reactant: 251183
is version of: GO:0045671
fast: false
reversible: true
name: Osteoclast removal
type: Reaction

metaid_0000038
unit: 251117
name: number
type: SBMLUnitsDef

metaid_0000008
constant: true
value: 3.0
type: Parameter

metaid_0000005
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 212.0
in compartment: metaid_0000003
name: Osteoblast
type: Species

251130
exponent: 1.0
scale: 0
multipler: 86400.0
kind: SECOND
type: SBMLUnit

metaid_0000034
event assignment: 251414
trigger: 251401
use values from trigger time: true
type: Event

metaid_0000030
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000003
name: Cells actively forming bone
type: Species

251183
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

metaid_0000015
constant: true
value: 0.0
type: Parameter

251117
exponent: 1.0
scale: 0
multipler: 1.0
kind: ITEM
type: SBMLUnit

metaid_0000019
constant: false
value: 0.0
type: Parameter

metaid_0000029
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000003
name: Cells actively resorbing bone
type: Species

metaid_0000010
constant: true
value: 0.2
type: Parameter

metaid_0000039
unit: 251130
name: day
type: SBMLUnitsDef

metaid_0000025
kinetic law: 251235
modifier: 251222
product: 251209
is version of: GO:0045669
fast: false
reversible: true
name: Osteoblast production
type: Reaction

251275
stoichiometry: 1.0
species: metaid_0000027
type: SpeciesReference

metaid_0000009
constant: true
value: 4.0
type: Parameter

251450
persistant: true
initial value: true
type: Trigger

metaid_0000033
event assignment: 251438
trigger: 251426
use values from trigger time: true
type: Event

metaid_0000006
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000003
name: Steady state osteoclast
type: Species

BIOMD0000000148
modified:
  W3 CDTF: Fri Apr 20 23:54:02 BST 2012
curated: true
reaction: metaid_0000025
parameter: metaid_0000015
rule: metaid_0000021
occurs in: http://identifiers.org/taxonomy/7711
parameter: metaid_0000012
species: metaid_0000030
is described by: http://identifiers.org/pubmed/14499354
rule: metaid_0000020
name: Komarova2003_BoneRemodeling
species: metaid_0000004
species: metaid_0000005
event: metaid_0000035
parameter: metaid_0000036
parameter: metaid_0000019
reaction: metaid_0000023
parameter: metaid_0000008
parameter: metaid_0000011
parameter: metaid_0000016
species: metaid_0000029
event: metaid_0000032
length unit: length
reaction: metaid_0000026
creator:
  ORG:
    orgname: California Institute of Technology
  n:
    given: Harish
    family: Dharuri
volume units: metaid_0000084
units def: metaid_0000038
parameter: metaid_0000013
time units: metaid_0000039
area units: metaid_0000005
notes: 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 Bone 2003 Aug;33(2):206-15 14499354 , Abstract: 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 …
parameter: metaid_0000037
event: metaid_0000033
parameter: metaid_0000009
parameter: metaid_0000017
species: metaid_0000027
reaction: metaid_0000024
parameter: metaid_0000014
compartment: metaid_0000003
is: MODEL6029826395
units def: metaid_0000039
created:
  W3 CDTF: Mon Jul 30 21:56:00 BST 2007
species: metaid_0000006
substance units: metaid_0000038
species: metaid_0000007
rule: metaid_0000022
reaction: metaid_0000028
is version of: GO:0046850
reaction: metaid_0000031
event: metaid_0000034
type: SBMLModel
parameter: metaid_0000010

metaid_0000016
constant: true
value: 0.24
type: Parameter

251249
stoichiometry: 1.0
species: metaid_0000005
type: SpeciesReference

metaid_0000023
kinetic law: 251170
modifier: 251157
product: 251143
is version of: GO:0045672
fast: false
reversible: true
name: Osteoclast production
type: Reaction

metaid_0000012
constant: true
value: 0.5
type: Parameter

metaid_0000026
kinetic law: 251262
reactant: 251249
is version of: GO:0045668
fast: false
reversible: true
name: Osteoblast removal
type: Reaction

251143
stoichiometry: 1.0
species: metaid_0000004
type: SpeciesReference

metaid_0000036
constant: false
value: 0.0
type: Parameter

251327
stoichiometry: 1.0
species: metaid_0000027
type: SpeciesReference

metaid_0000003
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

251426
persistant: true
initial value: true
type: Trigger

metaid_0000032
event assignment: 251389
trigger: 251377
notes: When the osteoclast number is greater than the steady state osteoclast number the flag is set to 1, this insures that in reaction R5, y1 is equal to the difference of x1 and x1_bar. When x1 is greater than x1_bar the difference is set to zero by setting the flag to zero. The same procedure is used for bone formation.
use values from trigger time: true
type: Event

metaid_0000007
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 0.0
in compartment: metaid_0000003
name: Steady state osteoblast
type: Species

metaid_0000017
constant: true
value: 0.0017
type: Parameter

metaid_0000013
constant: true
value: -0.5
type: Parameter

251377
persistant: true
initial value: true
type: Trigger

251401
persistant: true
initial value: true
type: Trigger

251209
stoichiometry: 1.0
species: metaid_0000005
type: SpeciesReference

metaid_0000027
constant: false
boundary condition: false
has only substance units: true
initial concentration: NaN
initial amount: 100.0
in compartment: metaid_0000003
name: Bone mass
type: Species

metaid_0000037
constant: false
value: 0.0
type: Parameter