Connective Tissue Growth Factor Enhances Osteoblastogenesis in Vitro

Smerdel-Ramoya, Anna; Zanotti, Stefano; Deregowski, Valérie; Canalis, Ernesto

doi:10.1074/jbc.m710140200

Cited by 49 publications

(56 citation statements)

References 60 publications

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“…These observations demonstrate that the skeletal effects of HES1 in osteoblasts are largely independent from those of Notch signaling (21,34,35). It is also important to note that the expression of Hes1 in skeletal cells is regulated by alternative signals, such as connective tissue growth factor, which induces Hes1 by mechanisms independent from Notch transactivation (24).…”

Section: Discussionmentioning

confidence: 99%

“…The fate of mesenchymal cells and their differentiation into osteoblasts is controlled by a signaling network that includes bone morphogenetic proteins, Wnt and Notch (18 -23). Notch signaling inhibits osteoblast differentiation and causes osteopenia in vivo, but even though HES1 is a target of Notch, it does not recapitulate all of the effects of Notch (24). HES1 participates in cell fate determination of mesenchymal multipotent cells and blocks the initial differentiation of preadipocytes, although it is necessary for their terminal differentiation (25,26).…”

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confidence: 99%

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HES1 (Hairy and Enhancer of Split 1) Is a Determinant of Bone Mass

Zanotti

Smerdel-Ramoya

Canalis

2011

Journal of Biological Chemistry

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HES1 (hairy and enhancer of split) is a transcription factor that regulates osteoblastogenesis in vitro. The skeletal effects of HES1 misexpression were studied. Transgenic mice where a 3.6-kilobase fragment of the collagen type 1 ␣1 promoter directs HES1 overexpression were created. Transgenics were osteopenic due to decreased osteoblast function in female and increased bone resorption in male mice. HES1 impaired osteoblastogenesis in vitro, and transgenic osteoblasts enhanced the resorptive activity of co-cultured osteoclast precursors. Mice homozygous for a Hes1 loxP-targeted allele were bred to transgenics, where the paired-related homeobox gene enhancer or the osteocalcin promoter direct Cre recombinase expression to inactivate Hes1 in the limb bud or in osteoblasts. To avoid genetic compensation, Hes1 was inactivated in the context of the global deletion of Hes3 and Hes5. Hes3 and Hes5 null mice had no skeletal phenotype. Hes1 inactivation in the limb bud increased femoral length and trabecular number. Hes1 inactivation in osteoblasts increased trabecular bone volume, number, and connectivity due to increased mineral apposition rate and suppressed bone resorption. Hes1 inactivation in vitro increased alkaline phosphatase expression and suppressed the resorptive activity of co-cultured osteoclast precursors. In conclusion, by inhibiting osteoblast function and inducing bone resorption, HES1 is an intracellular determinant of bone mass and structure.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

HES1 (Hairy and Enhancer of Split 1) Is a Determinant of Bone Mass

Zanotti

Smerdel-Ramoya

Canalis

2011

Journal of Biological Chemistry

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“…Also, since all of the CCN family members are highly interactive, direct interaction of CCN3 with CCN4 is considerable and thus should be investigated as well. In addition, CCN2 and CCN3 are reported to differentially regulate chondrocytes and osteoblasts via direct interaction with a common binding counterpart, bone morphogenetic protein 2, which is a critical molecule in cartilage and bone development (Canalis 2007;Smerdel-Ramoya et al 2008;Kawaki et al 2008Kawaki et al , 2011Maeda et al 2009). A similar molecular mechanism mediated by a common cofactor may thus be considered for understanding the regulation of fibrosis by CCN2 and CCN3.…”

Section: Discussionmentioning

confidence: 99%

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Kader

Kubota

Janune

et al. 2012

J. Cell Commun. Signal.

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CCN family proteins 2 and 3 (CCN2 and CCN3) belong to the CCN family of proteins, all having a high level of structural similarity. It is widely known that CCN2 is a profibrotic molecule that mediates the development of fibrotic disorders in many different tissues and organs. In contrast, CCN3 has been recently suggested to act as an anti-fibrotic factor in several tissues. This CCN3 action was shown earlier to be exerted by the repression of the CCN2 gene expression in kidney tissue, whereas different findings were obtained for liver cells. Thus, the molecular action of CCN3 yielding its anti-fibrotic effect is still controversial. Here, using a general model of fibrosis, we evaluated the effect of CCN3 overexpression on the gene expression of all of the CCN family members, as well as on that of fibrotic marker genes. As a result, repression of CCN2 gene expression was modest, while type I collagen and α-smooth muscle actin gene expression was prominently repressed. Interestingly, not only CCN2, but also CCN4 gene expression showed a decrease upon CCN3 overexpression. These findings indicate that fibrotic gene induction is under the control of a complex molecular network conducted by CCN family members functioning together.

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“…Recent studies have shown that Ccn2 is expressed in normal bones during development, growth, and remodeling, and treating osteoblast cultures with recombinant CCN2 enhances their proliferation and differentiation (Nishida et al 2000;Safadi et al 2003;Kubota and Takigawa 2011). According to another report, the overexpression of Ccn2 in ST-2 cells increased alkaline phosphatase activity, the mRNA levels of osteocalcin and alkaline phosphatase, and mineralized nodule formation (Smerdel-Ramoya et al 2008). These studies have collectively demonstrated that Ccn2 is expressed in bone tissue and that its gene product exerts diverse modulatory functions on osteoblast differentiation and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress

Honjo

Kubota

Kamioka

et al. 2012

J. Cell Commun. Signal.

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Fluid flow stress (FSS) is a major mechanical stress that induces bone remodeling upon orthodontic tooth movement, whereas CCN family protein 2 (CCN2) is a potent regenerator of bone defects. In this study, we initially evaluated the effect of laminar FSS on Ccn2 expression and investigated its mechanism in osteoblastic MC3T3-E1 cells. The Ccn2 expression was drastically induced by uniform FSS in an intensity dependent manner. Of note, the observed effect was inhibited by a Rho kinase inhibitor Y27632. Moreover, the inhibition of actin polymerization blocked the FSS-induced activation of Ccn2, whereas inducing Factin formation using cytochalasin D and jasplakinolide enhanced Ccn2 expression in the same cells. Finally, Factin formation was found to induce osteoblastic differentiation. In addition, activation of cyclic AMP-dependent kinase, which inhibits Rho signaling, abolished the effect of FSS. Collectively, these findings indicate the critical role of actin polymerization and Rho signaling in CCN2 induction and bone remodeling provoked by FSS.

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Connective Tissue Growth Factor Enhances Osteoblastogenesis in Vitro

Cited by 49 publications

References 60 publications

HES1 (Hairy and Enhancer of Split 1) Is a Determinant of Bone Mass

HES1 (Hairy and Enhancer of Split 1) Is a Determinant of Bone Mass

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress

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