Peterson2010 - Integrated calcium homeostasis and bone remodelling
Ontology highlight
ABSTRACT:
DISEASE(S): Hypoparathyroidism,Hyperparathyroidism
SUBMITTER: 
Vijayalakshmi Chelliah
PROVIDER: BIOMD0000000613 | BioModels | 2020-03-04
REPOSITORIES: BioModels
Publications
A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling.
Peterson Mark C MC Riggs Matthew M MM
Bone 20090902 1
Bone biology is physiologically complex and intimately linked to calcium homeostasis. The literature provides a wealth of qualitative and/or quantitative descriptions of cellular mechanisms, bone dynamics, associated organ dynamics, related disease sequela, and results of therapeutic interventions. We present a physiologically based mathematical model of integrated calcium homeostasis and bone biology constructed from literature data. The model includes relevant cellular aspects with major contr ...[more]
Similar Datasets
Project description:Parathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
2010-03-01 | GSE16983 | GEO
Project description:This a model from the article:
Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy.
Rattanakul C, Lenbury Y, Krishnamara N, Wollkind DJ.
Biosystems 2003:70(1):55-72.
12753937,
Abstract:
Bone, a major reservoir of body calcium, is under the hormonal control of the parathyroid hormone (PTH). Several aspects of its growth, turnover, and mechanism, occur in the absence of gonadal hormones. Sex steroids such as estrogen, nonetheless, play an important role in bone physiology, and are extremely essential to maintain bone balance in adults. In order to provide a basis for understanding the underlying mechanisms of bone remodeling as it is mediated by PTH, we propose here a mathematical model of the process. The nonlinear system model is then utilized to study the temporal effect of PTH as well as the action of estrogen replacement therapy on bone turnover. Analysis of the model is done on the assumption, supported by reported clinical evidence, that the process is characterized by highly diversified dynamics, which warrants the use of singular perturbation arguments. The model is shown to exhibit limit cycle behavior, which can develop into chaotic dynamics for certain ranges of the system's parametric values. Effects of estrogen and PTH administrations are then investigated by extending on the core model. Analysis of the model seems to indicate that the paradoxical observation that intermittent PTH administration causes net bone deposition while continuous administration causes net bone loss, and certain other reported phenomena may be attributed to the highly diversified dynamics which characterizes this nonlinear remodeling process.
This model was taken from the
CellML repository and automatically converted to SBML.
The original model was:
rattananakul, lenbury, krishnamara, wollkind. (2003) - version01
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2009-03-25 | BIOMD0000000274 | BioModels
Project description:Proctor2016 - Circadian rhythm of PTH and the
dynamics of signaling molecules on bone remodeling
This model is described in the article:
Simulated Interventions to
Ameliorate Age-Related Bone Loss Indicate the Importance of
Timing.
Proctor CJ, Gartland A.
Front Endocrinol (Lausanne) 2016; 7:
61
Abstract:
Bone remodeling is the continuous process of bone resorption
by osteoclasts and bone formation by osteoblasts, in order to
maintain homeostasis. The activity of osteoclasts and
osteoblasts is regulated by a network of signaling pathways,
including Wnt, parathyroid hormone (PTH), RANK
ligand/osteoprotegrin, and TGF-?, in response to stimuli, such
as mechanical loading. During aging there is a gradual loss of
bone mass due to dysregulation of signaling pathways. This may
be due to a decline in physical activity with age and/or
changes in hormones and other signaling molecules. In
particular, hormones, such as PTH, have a circadian rhythm,
which may be disrupted in aging. Due to the complexity of the
molecular and cellular networks involved in bone remodeling,
several mathematical models have been proposed to aid
understanding of the processes involved. However, to date,
there are no models, which explicitly consider the effects of
mechanical loading, the circadian rhythm of PTH, and the
dynamics of signaling molecules on bone remodeling. Therefore,
we have constructed a network model of the system using a
modular approach, which will allow further modifications as
required in future research. The model was used to simulate the
effects of mechanical loading and also the effects of different
interventions, such as continuous or intermittent
administration of PTH. Our model predicts that the absence of
regular mechanical loading and/or an impaired PTH circadian
rhythm leads to a gradual decrease in bone mass over time,
which can be restored by simulated interventions and that the
effectiveness of some interventions may depend on their
timing.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000612.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2016-05-26 | BIOMD0000000612 | BioModels
Project description:This a model from the article:
Mathematical model of paracrine interactions between osteoclasts and osteoblasts predicts anabolic action of parathyroid hormone on bone.
Komarova SV.
Endocrinology.2005 Aug;146(8):3589-95.
15860557,
Abstract:
To restore falling plasma calcium levels, PTH promotes calcium liberation from bone. PTH targets bone-forming cells, osteoblasts, to increase expression of the cytokine receptor activator of nuclear factor kappaB ligand (RANKL), which then stimulates osteoclastic bone resorption. Intriguingly, whereas continuous administration of PTH decreases bone mass, intermittent PTH has an anabolic effect on bone, which was proposed to arise from direct effects of PTH on osteoblastic bone formation. However, antiresorptive therapies impair the ability of PTH to increase bone mass, indicating a complex role for osteoclasts in the process. We developed a mathematical model that describes the actions of PTH at a single site of bone remodeling, where osteoclasts and osteoblasts are regulated by local autocrine and paracrine factors. It was assumed that PTH acts only to increase the production of RANKL by osteoblasts. As a result, PTH stimulated osteoclasts upon application, followed by compensatory osteoblast activation due to the coupling of osteoblasts to osteoclasts through local paracrine factors. Continuous PTH administration resulted in net bone loss, because bone resorption preceded bone formation at all times. In contrast, over a wide range of model parameters, short application of PTH resulted in a net increase in bone mass, because osteoclasts were rapidly removed upon PTH withdrawal, enabling osteoblasts to rebuild the bone. In excellent agreement with experimental findings, increase in the rate of osteoclast death abolished the anabolic effect of PTH on bone. This study presents an original concept for the regulation of bone remodeling by PTH, currently the only approved anabolic treatment for osteoporosis.
The model reproduces Figures 1B and 2A of the reference publication. To obtain the figures 1B, the parameter g21 needs changes. To obtain the figures 1A, the parameters g21, g12 and k2 need to changed. For details look at the curation tab.
The initial concentration of Osteoclasts (x1) is corrected to 1.06066 from 10.06066.
This model was taken from the
CellML repository and automatically converted to SBML.
The original model was:
CellMLdetails
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
The Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-11-23 | BIOMD0000000279 | BioModels
Project description:Pulmonary hypertension (PH) is an incurable right heart failure disease. Parathyroid hormone (PTH) is secreted from the parathyroid gland and plays a crucial role in calcium homeostasis. PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We assessed whether the regulation of PTH affected PH in a hypoxia (Hx)-induced PH mouse model. PTH treatment exacerbated right ventricular hypertrophy and right ventricular systolic pressure in Hx mice. Our data showed how is PTH effected for PH model murine lung.
2023-10-11 | GSE244861 | GEO
Project description:This a model from the article:
Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy.
Rattanakul C, Lenbury Y, Krishnamara N, Wollkind DJ. Biosystems
2003:70(1):55-72. 12753937
,
Abstract:
Bone, a major reservoir of body calcium, is under the hormonal control of the parathyroid hormone (PTH). Several aspects of its growth, turnover, and mechanism, occur in the absence of gonadal hormones. Sex steroids such as estrogen, nonetheless, play an important role in bone physiology, and are extremely essential to maintain bone balance in adults. In order to provide a basis for understanding the underlying mechanisms of bone remodeling as it is mediated by PTH, we propose here a mathematical model of the process. The nonlinear system model is then utilized to study the temporal effect of PTH as well as the action of estrogen replacement therapy on bone turnover. Analysis of the model is done on the assumption, supported by reported clinical evidence, that the process is characterized by highly diversified dynamics, which warrants the use of singular perturbation arguments. The model is shown to exhibit limit cycle behavior, which can develop into chaotic dynamics for certain ranges of the system's parametric values. Effects of estrogen and PTH administrations are then investigated by extending on the core model. Analysis of the model seems to indicate that the paradoxical observation that intermittent PTH administration causes net bone deposition while continuous administration causes net bone loss, and certain other reported phenomena may be attributed to the highly diversified dynamics which characterizes this nonlinear remodeling process.
About this model: This model represents the second model from the published paper (eqs 35-37). The model has been built on the core model (which describes changes in the concentration of PTH, the number of osteoclasts and the number of osteoblasts) by considering the effects of exogenous PTH administration - in this particular case pulsatile, for a period of 6 hours in an interval of 1 day. This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
rattananakul, lenbury, krishnamara, wollkind. (2003) - version01
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1012140000 | BioModels
Project description:This a model from the article:
Modeling of bone formation and resorption mediated by parathyroid hormone: response to estrogen/PTH therapy.
Rattanakul C, Lenbury Y, Krishnamara N, Wollkind DJ. Biosystems
2003:70(1):55-72. 12753937
,
Abstract:
Bone, a major reservoir of body calcium, is under the hormonal control of the parathyroid hormone (PTH). Several aspects of its growth, turnover, and mechanism, occur in the absence of gonadal hormones. Sex steroids such as estrogen, nonetheless, play an important role in bone physiology, and are extremely essential to maintain bone balance in adults. In order to provide a basis for understanding the underlying mechanisms of bone remodeling as it is mediated by PTH, we propose here a mathematical model of the process. The nonlinear system model is then utilized to study the temporal effect of PTH as well as the action of estrogen replacement therapy on bone turnover. Analysis of the model is done on the assumption, supported by reported clinical evidence, that the process is characterized by highly diversified dynamics, which warrants the use of singular perturbation arguments. The model is shown to exhibit limit cycle behavior, which can develop into chaotic dynamics for certain ranges of the system's parametric values. Effects of estrogen and PTH administrations are then investigated by extending on the core model. Analysis of the model seems to indicate that the paradoxical observation that intermittent PTH administration causes net bone deposition while continuous administration causes net bone loss, and certain other reported phenomena may be attributed to the highly diversified dynamics which characterizes this nonlinear remodeling process.
About this model: This model represents the third model from the published paper (eqs 38-40). The model has been built on the core model (which describes changes in the concentration of PTH, the number of osteoclasts and the number of osteoblasts) by considering the effects of exogenous Estrogen administration (for a period of 12 days in an interval of 28 days). This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
rattananakul, lenbury, krishnamara, wollkind. (2003) - version01
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@auckland.ac.nz
The University of Auckland
Auckland Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1012140001 | BioModels
Project description:Bone homeostasis is regulated by hormones such as parathyroid hormone (PTH). While PTH can stimulate osteo-progenitor expansion and bone synthesis, how the PTH-signaling intensity in progenitors is controlled is unclear. Endochondral bone osteoblasts arise from perichondrium-derived osteoprogenitors and hypertrophic chondrocytes (HC). We found, via single-cell transcriptomics, HC descendent cells activate membrane-type 1 metalloproteinase 14 (MMP14) and the PTH pathway as they transition to osteoblasts in neonatal and adult mice. Unlike Mmp14 global knockouts, postnatal day 10 (p10) HC lineage-specific Mmp14 null mutants (Mmp14ΔHC) produce more bone. Mechanistically, MMP14 cleaves the extracellular domain of PTH1R, dampening PTH signaling, and consistent with the implied regulatory role, in Mmp14ΔHC mutants, PTH signaling is enhanced. We found HC-derived osteoblasts contribute ~50% of osteogenesis promoted by treatment with PTH 1-34 and this response was amplified in Mmp14ΔHC. MMP14 control of PTH signaling likely applies also to both HC- and non-HC-derived osteoblasts because their transcriptomes are highly similar. Our study identifies a novel paradigm of MMP14 activity-mediated modulation of PTH signaling in the osteoblast lineage, contributing new insights into bone metabolism with therapeutic significance for bone-wasting diseases.
2023-03-13 | GSE222203 | GEO
Project description:Eric Hesse 9 Jan 2019, 17:34 (15 hours ago) to me, Hartmut Lieber Marcel, unten ist das abstract kopiert, reicht das? Lg, Eric Abstract Osteoporosis is caused by increased bone resorption and decreased bone formation. Intermittent administration of a fragment of Parathyroid hormone (PTH) activates osteoblast-mediated bone formation and is used in patients with severe osteoporosis. However, the mechanisms by which PTH elicits its anabolic effect are not fully elucidated. Here we show that the absence of the homeodomain protein TG-interacting factor 1 (Tgif1) impairs osteoblast differentiation and activity, leading to a reduced bone formation. Deletion of Tgif1 in osteoblasts and osteocytes decreases bone resorption due to an increased secretion of Semaphorin 3E (Sema3E), an osteoclast-inhibiting factor. Tgif1 is a PTH target gene and PTH treatment failed to increase bone formation and bone mass in Tgif1-deficient mice. Thus, our study identifies Tgif1 as a novel regulator of bone remodeling and an essential component of the PTH anabolic action. These insights contribute to a better understanding of bone metabolism and the anabolic function of PTH.
2019-01-29 | PXD012303 | Pride
Project description:This a model from the article:
Modeling the interactions between osteoblast and osteoclast activities in bone remodeling.
Lemaire V, Tobin FL, Greller LD, Cho CR, Suva LJ.
J Theor Biol.2004 Aug 7;229(3):293-309.
15234198,
Abstract:
We propose a mathematical model explaining the interactions between osteoblasts and osteoclasts, two cell types specialized in the maintenance of the bone integrity. Bone is a dynamic, living tissue whose structure and shape continuously evolves during life. It has the ability to change architecture by removal of old bone and replacement with newly formed bone in a localized process called remodeling. The model described here is based on the idea that the relative proportions of immature and mature osteoblasts control the degree of osteoclastic activity. In addition, osteoclasts control osteoblasts differentially depending on their stage of differentiation. Despite the tremendous complexity of the bone regulatory system and its fragmentary understanding, we obtain surprisingly good correlations between the model simulations and the experimental observations extracted from the literature. The model results corroborate all behaviors of the bone remodeling system that we have simulated, including the tight coupling between osteoblasts and osteoclasts, the catabolic effect induced by continuous administration of PTH, the catabolic action of RANKL, as well as its reversal by soluble antagonist OPG. The model is also able to simulate metabolic bone diseases such as estrogen deficiency, vitamin D deficiency, senescence and glucocorticoid excess. Conversely, possible routes for therapeutic interventions are tested and evaluated. Our model confirms that anti-resorptive therapies are unable to partially restore bone loss, whereas bone formation therapies yield better results. The model enables us to determine and evaluate potential therapies based on their efficacy. In particular, the model predicts that combinations of anti-resorptive and anabolic therapies provide significant benefits compared with monotherapy, especially for certain type of skeletal disease. Finally, the model clearly indicates that increasing the size of the pool of preosteoblasts is an essential ingredient for the therapeutic manipulation of bone formation. This model was conceived as the first step in a bone turnover modeling platform. These initial modeling results are extremely encouraging and lead us to proceed with additional explorations into bone turnover and skeletal remodeling.
This model corresponds to the core model published in the paper. There is no corresponding plot to reproduce for this model.
To obtain each of the 9 plots in the Figure 2 of the reference publication, there are some changes to be made to the core model.
The curation figure reproduces figure 2 of the reference publication. There is a corresponding SBML and Copasi files for each of the plot. See curation tab for more details.
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-11-18 | BIOMD0000000278 | BioModels