Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43
| Autor: | Klaus Willecke, Marcus Watkins, Vera Lúcia Szejnfeld, Dong Jin Chung, Roberto Civitelli, Charlles H. M. Castro, Min Young Chung, Joseph P. Stains, Martin Theis |
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| Rok vydání: | 2006 |
| Předmět: |
Peak bone mass
medicine.medical_specialty Anabolism Transgene Blotting Western Parathyroid hormone Mice Transgenic Biology Bone and Bones Mice Bone Density Osteogenesis Internal medicine medicine Teriparatide Animals Cell Proliferation Mice Knockout Osteoblasts Reverse Transcriptase Polymerase Chain Reaction Gap Junctions Osteoblast Cell Biology Apposition Phenotype Endocrinology medicine.anatomical_structure Parathyroid Hormone Connexin 43 cardiovascular system sense organs biological phenomena cell phenomena and immunity Gene Deletion Homeostasis medicine.drug |
| Zdroj: | Journal of Cell Science. 119:4187-4198 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | 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 Cx43fl allele and a 2.3-kb fragment of the α1(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. |
| Databáze: | OpenAIRE |
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