In:
Journal of Bone and Mineral Research, Wiley, Vol. 20, No. 4 ( 2005-04), p. 663-671
Abstract:
G s α is a ubiquitously expressed G protein α‐subunit that couples receptors to adenylyl cyclase. Mice with chondrocyte‐specific ablation of the G s α gene had severe epiphyseal and growth plate abnormalities and ectopic cartilage formation within the metaphyseal region of the tibia. These results show that G s α negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTH‐rP receptor in growth plate chondrocytes. Introduction: G s α is a ubiquitously expressed G protein α‐subunit that mediates signaling through G protein‐coupled receptors to activate the cAMP/protein kinase A signaling pathway. Although studies suggest an important role for G s α in regulating growth plate development, direct in vivo results examining this role are lacking. Materials and Methods: The G s α gene was ablated in murine cartilage by mating mice with loxP sites surrounding the G s α promoter and first exon with collagen 2a1 promoter‐Cre recombinase transgenic mice. Skeletal tissues were studied by gross and microscopic pathology, and gene expression was determined by in situ hybridization. Results and Conclusions: Mice with complete chondrocyte‐specific G s α deficiency (homozygotes) died within minutes after birth and had severe epiphyseal and growth plate defects with shortening of the proliferative zone and accelerated hypertrophic differentiation of growth plate chondrocytes, a phenotype similar to that of PTH/PTH‐related peptide (PTHrP) receptor knockout mice. Indian hedgehog and PTH/PTHrP receptor expression in prehypertrophic chondrocytes was unaffected in mutant mice. PTHrP expression in periarticular cartilage was increased in the mutant mice, probably because of the closer proximity of Ihh‐secreting chondrocytes to the periarticular zone. In addition, these mice developed ectopic cartilage at the anterior side of the metaphyseal region in the tibia. Mice with partial G s α deficiency (heterozygotes) exhibited no phenotype. These results show that G s α negatively regulates chondrocyte differentiation and is the critical signaling mediator of the PTH/PTHrP receptor in epiphyseal and growth plate chondrocytes.
Type of Medium:
Online Resource
ISSN:
0884-0431
,
1523-4681
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2008867-X
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