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Peterson2010 - Integrated calcium homeostasis and bone remodelling

ABSTRACT: Peterson2010 - integrated calcium homeostasis and bone remodelling This model is described in the article: A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling. Peterson MC, Riggs MM. Bone 2010 Jan; 46(1): 49-63 Abstract: 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 controlling mechanisms for bone remodeling and calcium homeostasis and appropriately describes a broad range of clinical and therapeutic conditions. These include changes in plasma parathyroid hormone (PTH), calcitriol, calcium and phosphate (PO4), and bone-remodeling markers as manifested by hypoparathyroidism and hyperparathyroidism, renal insufficiency, daily PTH 1-34 administration, and receptor activator of NF-kappaB ligand (RANKL) inhibition. This model highlights the utility of systems approaches to physiologic modeling in the bone field. The presented bone and calcium homeostasis model provides an integrated mathematical construct to conduct hypothesis testing of influential system aspects, to visualize elements of this complex endocrine system, and to continue to build upon iteratively with the results of ongoing scientific research. This model is hosted on BioModels Database and identified by: BIOMD0000000613. 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.

DISEASE(S): Hypoparathyroidism,Hyperparathyroidism

SUBMITTER: Vijayalakshmi Chelliah

PROVIDER: BIOMD0000000613 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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	BIOMD0000000613?filename=BIOMD0000000613-biopax2.owl	Owl
	BIOMD0000000613?filename=BIOMD0000000613-biopax3.owl	Owl
	BIOMD0000000613?filename=BIOMD0000000613.m	Other
	BIOMD0000000613?filename=BIOMD0000000613.png	Other
	BIOMD0000000613?filename=BIOMD0000000613.sci	Other

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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]

PMID: 19732857

Similar Datasets

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.

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.

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.

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.

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.