GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:21346198

From GONUTS
Jump to: navigation, search
Citation

Watkins, M, Grimston, SK, Norris, JY, Guillotin, B, Shaw, A, Beniash, E and Civitelli, R (2011) Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling. Mol. Biol. Cell 22:1240-51

Abstract

Connexin43 (Cx43) has an important role in skeletal homeostasis, and Cx43 gene (Gja1) mutations have been linked to oculodentodigital dysplasia (ODDD), a human disorder characterized by prominent skeletal abnormalities. To determine the function of Cx43 at early steps of osteogenesis and its role in the ODDD skeletal phenotype, we have used the Dermo1 promoter to drive Gja1 ablation or induce an ODDD mutation in the chondro-osteogenic linage. Both Gja1 null and ODDD mutant mice develop age-related osteopenia, primarily due to a progressive enlargement of the medullary cavity and cortical thinning. This phenotype is the consequence of a high bone turnover state, with increased endocortical osteoclast-mediated bone resorption and increased periosteal bone apposition. Increased bone resorption is a noncell autonomous defect, caused by exuberant stimulation of osteoclastogenesis by Cx43-deficient bone marrow stromal cells, via decreased Opg production. The latter is part of a broad defect in osteoblast differentiation and function, which also results in abnormal structural and material properties of bone leading to decreased resistance to mechanical load. Thus Cx43 in osteogenic cells is a critical regulator of both arms of the bone remodeling cycle, its absence causing structural changes remindful of aged or disused bone.

Links

PubMed PMC3078079 Online version:10.1091/mbc.E10-07-0571

Keywords

Age Factors; Animals; Bone Diseases, Developmental/genetics; Bone Diseases, Developmental/metabolism; Bone Remodeling/genetics; Bone Resorption/genetics; Bone Resorption/metabolism; Bone and Bones; Cell Communication; Cell Differentiation; Cells, Cultured; Connexin 43/deficiency; Connexin 43/genetics; Gene Expression; Genetic Association Studies; Humans; Mice; Mice, Transgenic; Mutation; Osteoblasts/cytology; Osteoblasts/metabolism; Osteogenesis/physiology; Osteoprotegerin/antagonists & inhibitors; Osteoprotegerin/genetics; Osteoprotegerin/metabolism; Phenotype; Promoter Regions, Genetic; Stromal Cells/cytology; Stromal Cells/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CXA1

acts_upstream_of_or_within

GO:0030500: regulation of bone mineralization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2445468
MGI:MGI:3776013

P

Seeded From UniProt

complete

MOUSE:CXA1

acts_upstream_of_or_within

GO:0046850: regulation of bone remodeling

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2445468
MGI:MGI:3776013

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.