Connective tissue growth factor is required for skeletal development and postnatal skeletal homeostasis in male mice.
Document Type
Article
Publication Date
2010
Keywords
Bone-Density, Bone-and-Bones, Cells-Cultured, Connective-Tissue-Growth-Factor, Enhancer-Elements-Genetic, Growth-and-Development, Homeodomain-Proteins, Homeostasis, Mice-Inbred-C57BL, Mice-Transgenic, Osteoblasts, Osteocalcin, Osteogenesis, Sex-Characteristics
First Page
3490
Last Page
3501
JAX Source
Endocrinology 2010 Aug; 151(8):3490-501.
Abstract
Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf(+/LacZ) heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf(+/LacZ) heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis.
Recommended Citation
Canalis E,
Zanotti S,
Beamer WG,
Economides AN,
Smerdel RA.
Connective tissue growth factor is required for skeletal development and postnatal skeletal homeostasis in male mice. Endocrinology 2010 Aug; 151(8):3490-501.