Implementación del modelo de remodelación ósea de Komarova para el estudio de la sensibilidad del proceso de remodelamiento óseo ante cambios en factores locales
Main Article Content
Keywords
remodelación, hueso compacto, metástasis ósea, osteoclastos, osteoblastos, osteoprotegerina, PTH, TGF
Resumen
En este artículo se lleva a cabo la implementación del modelo de remodelación ósea de nivel celular planteado por Komarova, usando como herramienta un diagrama de bloques funcionales. El objetivo de esta implementación es hacer un análisis de sensibilidad con respecto a la variación de los parámetros del modelo y determinar la influencia de los factores paracrinos y autocrinos en la formación de osteoclastos y osteoblastos. El modelo se implementó en el paquete comercial Simulink de Matlab R2007b. Se encontró que cada parámetro tiene un rango de funcionamiento bien determinado y que, fuera de él, la estabilidad se pierde y se establecen ganancias o pérdidas de masa ósea que se pueden atribuir a anormalidades sistémicas de los huesos. Este trabajo constituye un avance sobre el tema de remodelación ósea gracias a que, a diferencia de trabajos previos, se incluyen las variaciones de los parámetros propios del proceso de remodelación que llevan a posibles alteraciones de los procesos del metabolismo óseo, lo cual constituye un punto de partida para el estudio de enfermedades y alteraciones de la densidad del hueso, y permite iniciar el modelado de nuevas enfermedades relacionadas con los huesos, como es, por ejemplo, la metástasis ósea. Este estudio, entonces, es un avance con respecto a los trabajos presentados por Komarova y Lemaire y puede explicar fenómenos de metástasis y alteraciones metabólicas como los descritos en Manolagas.
PACS: 87.85.gj
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Referencias
[1] Svetlana V. Komarova, Robert J. Smith, Jeffrey Dixon S., Stephen M. Sims and Lindi M.Wahl. Mathematical model predicts a critical role for osteoclast autocrine regulation in the control of bone remodeling. Bone, ISSN 8756–3282, 33(2), 206– 215 (2003).
[2] Vincent Lemairea, Frank L. Tobina, Larry D. Grellera, Carolyn R. Choa and Larry J. Suva. Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. Journal of Theoretical Biology, ISSN 0022–5193, 229(3), 293–309 (2004).
[3] Stavros C. Manolagas. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Reviews, ISSN 0163–769X, eISSN
[4] Marco G. Cecchinia, Antoinette Wetterwalda, Gabri van der Pluijmb and George N. Thalmanna. Molecular and Biological Mechanisms of Bone Metastasis. EAU– EBU, ISSN 1871–2592, 3(4), 214–226 (2005).
[5] Adam Moroz, Martin C. Crane, Geoff Smith and David I. Wimpenny. Phenomenological model of bone remodeling cycle containing osteocyte regulation loop. BioSystems, ISSN 0303–2647, 84(3), 183–190 (2006).
[6] David Ian Wimpenny and Adam Moroz. On allosteric control model of bone turnover cycle containing osteocyte regulation loop. BioSystems, ISSN 0303–2647, 90(2), 295–308 (2007).
[7] Ernesto Canalis and Donato Agnusdei. Insulin–like growth factors and their role in osteoporosis. Calcified Tissue International , pISSN 0171–967X, eISSN 1432– 0827, 58(3), 58–133–4 (1996).
[8] I. Fernández–Tresguerres,M. A. Alobera, M. C. Pingarrón and Luis Blanco. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.Medicina oral patologia oral y cirugia bucal, ISSN 1698–4447, 11(1), 32–36 (2006).
[9] J. D. Termine. Bone Matrix Proteins and Mineralization Process. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3.Raven Press, Favus M. J., New York, 21–24 (1993).
[10] J. González Macías y S. Serrano Figueras. Enfermedades óseas. En Farreras P, ed. Medicina Interna, decimotercera edición, Madrid: Mosby–Doyma, 1064–1089 (1995).
[11] Jane B. Lian and Gary S. Stein. Concepts of osteoblast growth and differentia- tion: Basis for modulation of bone cell development and tissue formation. Critical Reviews in Oral Biology & Medicine, pISSN 1045–4411, eISSN 1544–1113, 3(3), 269–305 (1992).
[12] J. E. Puzas. The Osteoblast. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3. Raven Press, Favus M. J., New York, 15–20 (1993).
[13] T. A. Owen et al. Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix . Journal of Cellular Physiology, ISSN 0021–9541, 143(3), 420–430 (1990).
[14] J. E. Aubin, K. Turksen and J. N. M. Hersche. Osteoblastic cell Lineage. En Noda M, Cellular and Molecular Biology of Bone, ISBN 978–0–12–520225–1. Academic Press Inc, San Diego, 1–45 (1993).
[15] A. M. Parfitt. Osteonal and hemi–osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. Journal of cellular biochemistry, ISSN 0730–2312, 55(3), 273–286 (1994).
[16] J. F. Mikán y W. D. Oliveros. Osteoclastogénesis y Enfermedades óseas. Revista Med, ISSN 0121–5256, 15(2), 261–270 (2007).
[17] S. Serrano, J. Aubia y M. L. Mariñoso. Bases histológicas de la histomorfometría ósea. En Patología Osea Metabólica, ISBN 84–8536–002–8. Barcelona: Doyma, 55–70 (1990).
[18] D. J. Hadjidakis and I. I. Androulakis. Bone Remodeling. Annals New York Academy of Sciences, ISSN 0077–8923, 1092, 385–396 (2006).
[19] E. F. Eriksen, D. W. Axelrod and F. Melsen. Bone histology and bone histomorphometry. En Bone Histomorphometry, ISBN 10 0781701228. Raven Press, Nueva York, 33–48 (1994).
[20] A. M. Gurley and S. I. Roth. Bone. En Histology for Pathologists, ISBN 0– 88167–621–7, Raven Press, New York, 61–80 (1992). Referenciado en 114
[21] M. Petrt´yl, J. Hert and P. Fiala. Spatial organization of the haversian bone in man. Journal of Biomechanics, pISSN 0021–9290, eISSN 1873–2380, 29(2), 161–169 (1996).
[22] S. C. Manolagas and R. L. Jilka. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. The New England journal of medicine, pISSN 0028–4793, eISSN 1533–4406, 332(5), 305–311 (1995).
[23] G. Gutiérrez. Regulación paracrina del hueso. En Manual práctico de osteoporosis y enfermedades del metabolismo mineral , 13–18 (2004).
[24] Ja Elías, W. Tang and M. C. Howitz. Cytokine and Hormonal stimulation of human osteosarcoma cytokine–11 production. Endocrinology, pISSN 0013–7227, eISSN 1945–7170, 136, 489–498 (1995).
[25] P. Watson, D. Lazowski, V. Han, L. Fraher, B. Steer and A. Hodsman. Parathyroid hormone restores bone mass and enhances osteoblast insulin–like growth factor I gene expression in ovariectomized rats. Bone, ISSN 8756–3282, 16(3), 357–365 (1995).
[26] J. Pfeilschifter et al. Parathyroid hormone increases the concentration of insuline–like growth factor I and transforming growth factor beta 1 in rat bone. The Journal of Clinical Investigation, eISSN 0021–9738,, eISSN 1558–8238, 96, 767–774 (1995).
[27] H. M. Frost. The mechanostat: a proposed pathogenic mechanism of osteoporosis and the bone mass effects of mechanical and nonmechanical agents. Bone and Mineral, ISSN 0169–6009, 2, 73–85 (1987). Referenciado en 116 [28] H. Weinans, R. Huiskes and H. J. Grootenboer. The behavior of adaptive bone–remodeling simulation models. Biomechanics, ISSN 0021–9290, 25(12), 1425–1441 (1992).
[29] M. H. Kroll. Parathyroid hormone temporal effects on bone formation and resorption. Bulletin of Mathematical Biology, pISSN 0092–8240, eISSN 1522–9602, 62(1), 163–188 (2000).
[30] S. V. Komarova. Mathematical Model of Paracrine Interactions between Osteoclasts and Osteoblasts Predicts Anabolic Action of Parathyroid Hormone on Bone. Endocrinology, pISSN 0013–7227, eISSN 1945–7170, 146(8), 3589–3595 (2005).
[31] G. R. Mundy. Bone Resorbing Cells. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3. Raven Press, Favus M. J., New York, 25–32 (1993).
[32] Yi Jun Yang. Histology of Bone: Multimedia, Media file 13. http://emedicine.medscape.com/article/1254517–media.
[2] Vincent Lemairea, Frank L. Tobina, Larry D. Grellera, Carolyn R. Choa and Larry J. Suva. Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. Journal of Theoretical Biology, ISSN 0022–5193, 229(3), 293–309 (2004).
[3] Stavros C. Manolagas. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Reviews, ISSN 0163–769X, eISSN
[4] Marco G. Cecchinia, Antoinette Wetterwalda, Gabri van der Pluijmb and George N. Thalmanna. Molecular and Biological Mechanisms of Bone Metastasis. EAU– EBU, ISSN 1871–2592, 3(4), 214–226 (2005).
[5] Adam Moroz, Martin C. Crane, Geoff Smith and David I. Wimpenny. Phenomenological model of bone remodeling cycle containing osteocyte regulation loop. BioSystems, ISSN 0303–2647, 84(3), 183–190 (2006).
[6] David Ian Wimpenny and Adam Moroz. On allosteric control model of bone turnover cycle containing osteocyte regulation loop. BioSystems, ISSN 0303–2647, 90(2), 295–308 (2007).
[7] Ernesto Canalis and Donato Agnusdei. Insulin–like growth factors and their role in osteoporosis. Calcified Tissue International , pISSN 0171–967X, eISSN 1432– 0827, 58(3), 58–133–4 (1996).
[8] I. Fernández–Tresguerres,M. A. Alobera, M. C. Pingarrón and Luis Blanco. Physiological bases of bone regeneration I. Histology and physiology of bone tissue.Medicina oral patologia oral y cirugia bucal, ISSN 1698–4447, 11(1), 32–36 (2006).
[9] J. D. Termine. Bone Matrix Proteins and Mineralization Process. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3.Raven Press, Favus M. J., New York, 21–24 (1993).
[10] J. González Macías y S. Serrano Figueras. Enfermedades óseas. En Farreras P, ed. Medicina Interna, decimotercera edición, Madrid: Mosby–Doyma, 1064–1089 (1995).
[11] Jane B. Lian and Gary S. Stein. Concepts of osteoblast growth and differentia- tion: Basis for modulation of bone cell development and tissue formation. Critical Reviews in Oral Biology & Medicine, pISSN 1045–4411, eISSN 1544–1113, 3(3), 269–305 (1992).
[12] J. E. Puzas. The Osteoblast. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3. Raven Press, Favus M. J., New York, 15–20 (1993).
[13] T. A. Owen et al. Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix . Journal of Cellular Physiology, ISSN 0021–9541, 143(3), 420–430 (1990).
[14] J. E. Aubin, K. Turksen and J. N. M. Hersche. Osteoblastic cell Lineage. En Noda M, Cellular and Molecular Biology of Bone, ISBN 978–0–12–520225–1. Academic Press Inc, San Diego, 1–45 (1993).
[15] A. M. Parfitt. Osteonal and hemi–osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. Journal of cellular biochemistry, ISSN 0730–2312, 55(3), 273–286 (1994).
[16] J. F. Mikán y W. D. Oliveros. Osteoclastogénesis y Enfermedades óseas. Revista Med, ISSN 0121–5256, 15(2), 261–270 (2007).
[17] S. Serrano, J. Aubia y M. L. Mariñoso. Bases histológicas de la histomorfometría ósea. En Patología Osea Metabólica, ISBN 84–8536–002–8. Barcelona: Doyma, 55–70 (1990).
[18] D. J. Hadjidakis and I. I. Androulakis. Bone Remodeling. Annals New York Academy of Sciences, ISSN 0077–8923, 1092, 385–396 (2006).
[19] E. F. Eriksen, D. W. Axelrod and F. Melsen. Bone histology and bone histomorphometry. En Bone Histomorphometry, ISBN 10 0781701228. Raven Press, Nueva York, 33–48 (1994).
[20] A. M. Gurley and S. I. Roth. Bone. En Histology for Pathologists, ISBN 0– 88167–621–7, Raven Press, New York, 61–80 (1992). Referenciado en 114
[21] M. Petrt´yl, J. Hert and P. Fiala. Spatial organization of the haversian bone in man. Journal of Biomechanics, pISSN 0021–9290, eISSN 1873–2380, 29(2), 161–169 (1996).
[22] S. C. Manolagas and R. L. Jilka. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. The New England journal of medicine, pISSN 0028–4793, eISSN 1533–4406, 332(5), 305–311 (1995).
[23] G. Gutiérrez. Regulación paracrina del hueso. En Manual práctico de osteoporosis y enfermedades del metabolismo mineral , 13–18 (2004).
[24] Ja Elías, W. Tang and M. C. Howitz. Cytokine and Hormonal stimulation of human osteosarcoma cytokine–11 production. Endocrinology, pISSN 0013–7227, eISSN 1945–7170, 136, 489–498 (1995).
[25] P. Watson, D. Lazowski, V. Han, L. Fraher, B. Steer and A. Hodsman. Parathyroid hormone restores bone mass and enhances osteoblast insulin–like growth factor I gene expression in ovariectomized rats. Bone, ISSN 8756–3282, 16(3), 357–365 (1995).
[26] J. Pfeilschifter et al. Parathyroid hormone increases the concentration of insuline–like growth factor I and transforming growth factor beta 1 in rat bone. The Journal of Clinical Investigation, eISSN 0021–9738,, eISSN 1558–8238, 96, 767–774 (1995).
[27] H. M. Frost. The mechanostat: a proposed pathogenic mechanism of osteoporosis and the bone mass effects of mechanical and nonmechanical agents. Bone and Mineral, ISSN 0169–6009, 2, 73–85 (1987). Referenciado en 116 [28] H. Weinans, R. Huiskes and H. J. Grootenboer. The behavior of adaptive bone–remodeling simulation models. Biomechanics, ISSN 0021–9290, 25(12), 1425–1441 (1992).
[29] M. H. Kroll. Parathyroid hormone temporal effects on bone formation and resorption. Bulletin of Mathematical Biology, pISSN 0092–8240, eISSN 1522–9602, 62(1), 163–188 (2000).
[30] S. V. Komarova. Mathematical Model of Paracrine Interactions between Osteoclasts and Osteoblasts Predicts Anabolic Action of Parathyroid Hormone on Bone. Endocrinology, pISSN 0013–7227, eISSN 1945–7170, 146(8), 3589–3595 (2005).
[31] G. R. Mundy. Bone Resorbing Cells. En Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, second edition, ISBN 0–7817–0083–3. Raven Press, Favus M. J., New York, 25–32 (1993).
[32] Yi Jun Yang. Histology of Bone: Multimedia, Media file 13. http://emedicine.medscape.com/article/1254517–media.