Functional requirement of CCN2 for intramembranous bone formation in embryonic mice.
CCN2 is best known as a promoter of chondrocyte differentiation among the CCN family members, and Ccn2 null mutant mice display skeletal dysmorphisms. However, little is known concerning the roles of CCN2 during bone formation. We herein present a comparative analysis of wild-type and Ccn2 null mice to investigate the roles of CCN2 in bone development. Multiple histochemical methods were employed to analyze the effects of CCN2 deletion in vivo, and effects of CCN2 on the osteogenic response were evaluated with the isolated and cultured osteoblasts. As a result, we found a drastic reduction of the osteoblastic phenotype in Ccn2 null mutants. Importantly, addition of exogenous CCN2 promoted every step of osteoblast differentiation and rescued the attenuated activities of the Ccn2 null osteoblasts. These results suggest that CCN2 is required not only for the regulation of cartilage and subsequent events, but also for the normal intramembranous bone development.
Kawaki
Harumi
H
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Kubota
Satoshi
S
Suzuki
Akiko
A
Yamada
Tomohiro
T
Matsumura
Tatsushi
T
Mandai
Toshiko
T
Yao
Mayumi
M
Maeda
Takeyasu
T
Lyons
Karen M
KM
Takigawa
Masaharu
M
D000818:Animals; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice / Q000196:embryology* / Q000378:metabolism*; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor