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Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43
- Source :
- Journal of Cell Science. 119:4187-4198
- Publication Year :
- 2006
- Publisher :
- The Company of Biologists, 2006.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14779137 and 00219533
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Science
- Accession number :
- edsair.doi.dedup.....6c676c1fe7f20245212bbb0df2c4ac8b