BIOMD0000000148
type: SBMLModel
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
creator:
  ORG:
    orgname: California Institute of Technology
  n:
    given: Harish
    family: Dharuri
parameter: metaid_0000008
parameter: metaid_0000011
parameter: metaid_0000016
species: metaid_0000029
event: metaid_0000032
length unit: length
reaction: metaid_0000026
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
species: metaid_0000006
substance units: metaid_0000038
species: metaid_0000007
created:
  W3 CDTF: Mon Jul 30 21:56:00 BST 2007
rule: metaid_0000022
reaction: metaid_0000028
is version of: GO:0046850
reaction: metaid_0000031
event: metaid_0000034
parameter: metaid_0000010

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

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

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

251209
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000005

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

metaid_0000015
type: Parameter
constant: true
value: 0.0

metaid_0000012
type: Parameter
constant: true
value: 0.5

metaid_0000030
type: Species
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

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

metaid_0000037
type: Parameter
constant: false
value: 0.0

251450
type: Trigger
persistant: true
initial value: true

metaid_0000036
type: Parameter
constant: false
value: 0.0

metaid_0000019
type: Parameter
constant: false
value: 0.0

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

251143
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004

metaid_0000008
type: Parameter
constant: true
value: 3.0

metaid_0000011
type: Parameter
constant: true
value: 0.02

metaid_0000016
type: Parameter
constant: true
value: 0.24

metaid_0000029
type: Species
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

metaid_0000032
type: Event
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

251377
type: Trigger
persistant: true
initial value: true

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

251249
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000005

metaid_0000038
type: SBMLUnitsDef
unit: 251117
name: number

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

metaid_0000013
type: Parameter
constant: true
value: -0.5

metaid_0000039
type: SBMLUnitsDef
unit: 251130
name: day

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

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

251426
type: Trigger
persistant: true
initial value: true

metaid_0000009
type: Parameter
constant: true
value: 4.0

metaid_0000017
type: Parameter
constant: true
value: 0.0017

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

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

251183
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000004

metaid_0000014
type: Parameter
constant: true
value: 1.0

metaid_0000006
type: Species
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

metaid_0000007
type: Species
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

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

251275
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000027

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

251327
type: SpeciesReference
stoichiometry: 1.0
species: metaid_0000027

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

251401
type: Trigger
persistant: true
initial value: true

metaid_0000010
type: Parameter
constant: true
value: 0.2