Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2006 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNIFESP |
| dARK ID: | ark:/48912/001300000pmkk |
| Texto Completo: | http://dx.doi.org/10.1242/jcs.03162 http://repositorio.unifesp.br/handle/11600/29209 |
Resumo: | Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43(fl) allele and a 2.3-kb fragment of the alpha(I)(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43(-/fl) mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43(+/fl) mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43(-/fl) mice, with Cx43(-/fl) exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre; Cx43(-/fl), despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. in conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism. |
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Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43gap junctionsconnexin43teriparatidebone anabolic agentsconditional gene deletionConnexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43(fl) allele and a 2.3-kb fragment of the alpha(I)(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43(-/fl) mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43(+/fl) mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43(-/fl) mice, with Cx43(-/fl) exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre; Cx43(-/fl), despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. in conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism.Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63110 USAChonnam Natl Univ, Sch Med, Dept Internal Med, Res Inst Med Sci, Kwangju, South KoreaUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilUniv Bonn, Inst Genet, D-5300 Bonn, GermanyUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of ScienceCompany of Biologists LtdWashington UnivChonnam Natl UnivUniversidade Federal de São Paulo (UNIFESP)Univ BonnChung, Dong JinCastro, Charlles Heldan de Moura [UNIFESP]Watkins, MarcusStains, Joseph P.Chung, Min YoungSzejnfeld, Vera Lucia [UNIFESP]Willecke, KlausTheis, MartinCivitelli, Roberto2016-01-24T12:41:32Z2016-01-24T12:41:32Z2006-10-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion4187-4198application/pdfhttp://dx.doi.org/10.1242/jcs.03162Journal of Cell Science. Cambridge: Company of Biologists Ltd, v. 119, n. 20, p. 4187-4198, 2006.10.1242/jcs.03162WOS000241217100006.pdf0021-9533http://repositorio.unifesp.br/handle/11600/29209WOS:000241217100006ark:/48912/001300000pmkkengJournal of Cell Scienceinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-07T13:24:35Zoai:repositorio.unifesp.br/:11600/29209Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:29:37.929087Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.none.fl_str_mv |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| title |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| spellingShingle |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 Chung, Dong Jin gap junctions connexin43 teriparatide bone anabolic agents conditional gene deletion |
| title_short |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| title_full |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| title_fullStr |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| title_full_unstemmed |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| title_sort |
Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 |
| author |
Chung, Dong Jin |
| author_facet |
Chung, Dong Jin Castro, Charlles Heldan de Moura [UNIFESP] Watkins, Marcus Stains, Joseph P. Chung, Min Young Szejnfeld, Vera Lucia [UNIFESP] Willecke, Klaus Theis, Martin Civitelli, Roberto |
| author_role |
author |
| author2 |
Castro, Charlles Heldan de Moura [UNIFESP] Watkins, Marcus Stains, Joseph P. Chung, Min Young Szejnfeld, Vera Lucia [UNIFESP] Willecke, Klaus Theis, Martin Civitelli, Roberto |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Washington Univ Chonnam Natl Univ Universidade Federal de São Paulo (UNIFESP) Univ Bonn |
| dc.contributor.author.fl_str_mv |
Chung, Dong Jin Castro, Charlles Heldan de Moura [UNIFESP] Watkins, Marcus Stains, Joseph P. Chung, Min Young Szejnfeld, Vera Lucia [UNIFESP] Willecke, Klaus Theis, Martin Civitelli, Roberto |
| dc.subject.por.fl_str_mv |
gap junctions connexin43 teriparatide bone anabolic agents conditional gene deletion |
| topic |
gap junctions connexin43 teriparatide bone anabolic agents conditional gene deletion |
| description |
Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43(fl) allele and a 2.3-kb fragment of the alpha(I)(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43(-/fl) mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43(+/fl) mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43(-/fl) mice, with Cx43(-/fl) exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre; Cx43(-/fl), despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. in conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism. |
| publishDate |
2006 |
| dc.date.none.fl_str_mv |
2006-10-15 2016-01-24T12:41:32Z 2016-01-24T12:41:32Z |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1242/jcs.03162 Journal of Cell Science. Cambridge: Company of Biologists Ltd, v. 119, n. 20, p. 4187-4198, 2006. 10.1242/jcs.03162 WOS000241217100006.pdf 0021-9533 http://repositorio.unifesp.br/handle/11600/29209 WOS:000241217100006 |
| dc.identifier.dark.fl_str_mv |
ark:/48912/001300000pmkk |
| url |
http://dx.doi.org/10.1242/jcs.03162 http://repositorio.unifesp.br/handle/11600/29209 |
| identifier_str_mv |
Journal of Cell Science. Cambridge: Company of Biologists Ltd, v. 119, n. 20, p. 4187-4198, 2006. 10.1242/jcs.03162 WOS000241217100006.pdf 0021-9533 WOS:000241217100006 ark:/48912/001300000pmkk |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Journal of Cell Science |
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info:eu-repo/semantics/openAccess |
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openAccess |
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4187-4198 application/pdf |
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Company of Biologists Ltd |
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Company of Biologists Ltd |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
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