The skeletal site-specific role of connective tissue growth factor in prenatal osteogenesis.

Lambi AG, Pankratz TL, Mundy C, Gannon M, Barbe MF, Richtsmeier JT, Popoff SN
Dev Dyn. 2012 241 (12): 1944-59

PMID: 23073844 · PMCID: PMC3752831 · DOI:10.1002/dvdy.23888

BACKGROUND - Connective tissue growth factor (CTGF/CCN2) is a matricellular protein that is highly expressed during bone development. Mice with global CTGF ablation (knockout, KO) have multiple skeletal dysmorphisms and perinatal lethality. A quantitative analysis of the bone phenotype has not been conducted.

RESULTS - We demonstrated skeletal site-specific changes in growth plate organization, bone microarchitecture, and shape and gene expression levels in CTGF KO compared with wild-type mice. Growth plate malformations included reduced proliferation zone and increased hypertrophic zone lengths. Appendicular skeletal sites demonstrated decreased metaphyseal trabecular bone, while having increased mid-diaphyseal bone and osteogenic expression markers. Axial skeletal analysis showed decreased bone in caudal vertebral bodies, mandibles, and parietal bones in CTGF KO mice, with decreased expression of osteogenic markers. Analysis of skull phenotypes demonstrated global and regional differences in CTGF KO skull shape resulting from allometric (size-based) and nonallometric shape changes. Localized differences in skull morphology included increased skull width and decreased skull length. Dysregulation of the transforming growth factor-β-CTGF axis coupled with unique morphologic traits provides a potential mechanistic explanation for the skull phenotype.

CONCLUSIONS - We present novel data on a skeletal phenotype in CTGF KO mice, in which ablation of CTGF causes site-specific aberrations in bone formation.

Copyright © 2012 Wiley Periodicals, Inc.

MeSH Terms (11)

Animals Antigens, Differentiation Cell Proliferation Connective Tissue Growth Factor Growth Plate Mice Mice, Knockout Organ Specificity Osteogenesis Skull Spine

Connections (2)

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