Translational Regulation Is a Control Point in RUNX2/Cbfa1 Gene Expression

Sivasubramaniam, Sudhakar; Li, Ye; Katz, Michael; Elango, Narayanasamy

doi:10.1006/bbrc.2001.6033

Cited by 54 publications

(48 citation statements)

References 37 publications

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“…Scale bar, 80 µm. 1999), is involved in the effect of MyoD on BMP-7-induced osteogenesis, we confirmed that Runx2/Cbfa1 is expressed in C3H10T1/2 cultures because the expression of this protein has been shown to be under translational control (Sudhakar et al, 2001). Whereas Runx2/Cbfa1 was not detected in cultures at day zero (D0), protein was expressed after 3 days in low mitogen media with or without BMP-7 treatment (Fig.…”

Section: Myod Enhances Osteogenic Differentiation Induced By Runx2/cbfa1supporting

confidence: 71%

MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures

Komaki

Asakura

Rudnicki

et al. 2004

Journal of Cell Science

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The muscle-specific, basic helix-loop-helix transcription factor MyoD can induce cells from other mesenchymal lineages to express a skeletal muscle phenotype. Interestingly, MyoD is initially upregulated in myogenic cells incubated with bone morphogenetic proteins (BMPs), a treatment that induces osteogenic differentiation, suggesting that MyoD has a role in BMP-induced osteogenesis of myogenic cells. This possibility is supported by our observations that muscle satellite cells derived from adult MyoD-/- mice show severely impaired osteogenic induction by BMP-7 (osteogenic protein 1; OP-1) as indicated by the decreased gene expression of the bone markers alkaline phosphatase, osteocalcin, Runx2/Cbfa1, and Osterix. Ectopic expression of MyoD increased alkaline phosphatase activity and Osterix mRNA expression in response to BMP treatment. Similarly, ectopic expression of MyoD in the pluripotent mesenchymal cell line C3H10T1/2 increased alkaline phosphatase activity induced by BMP-7. Transcription assays showed that transfection with a MyoD-expression vector, but not other myogenic basic helix-loop-helix transcription factors (Myf5, myogenin) increased Runx2/Cbfa1 transactivation of a reporter gene construct containing either six OSE sequences in tandem or a single OSE site. This effect was enhanced by BMP treatment. These studies, therefore, demonstrate that the muscle transcription factor MyoD is required for efficient BMP-induced osteogenesis of myogenic cells and indicate that MyoD might exert its effects through co-operative interactions with Runx2/Cbfa1.

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Section: Myod Enhances Osteogenic Differentiation Induced By Runx2/cbfa1supporting

confidence: 71%

MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures

Komaki

Asakura

Rudnicki

et al. 2004

Journal of Cell Science

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“…Cbfa1 mRNA is constitutively expressed in osteoblasts and in osteoblast precursors and fibroblasts, whereas cbfa1 protein could only be detected in differentiated osteoblasts. 37,38 The aortic expression of cbfa1 protein also went along with the early stages of calcification in uremic rats receiving high PTH infusion 41 and in uremic mice receiving a high phosphorus diet. 42 Furthermore, the expression of osteochondrogenic transcription factor cbfa1 is not restricted to osteoblasts.…”

Section: Discussionmentioning

confidence: 97%

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

Neven

Persy

Dauwe

et al. 2010

ATVB

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Objective-To investigate cell biological changes in calcified aortas of rats that experienced chronic renal failure. Methods and Results-Vascular smooth muscle cells have the potential to transdifferentiate to either chondrocytes or osteoblasts, depending on the molecular pathways that are stimulated. Uremia-related medial calcification was induced by feeding rats an adenine low-protein diet for 4 weeks. Aortic calcification was evaluated biochemically and histochemically and with in vivo micro-computed tomographic scanning. Immunohistochemistry and RT-PCR were applied to analyze the time-dependent aortic expression of molecules involved in the segregation between the chondrocyte versus osteoblast differentiation pathway. After 4 weeks, 85% of the uremic rats had developed distinct aortic medial calcification, which increased to severely calcified lesions during further follow-up. The calcification process was accompanied by a significant time-dependent increase in the expression of the chondrocyte-specific markers sex determining region Y-box 9 (sox9), collagen II, and aggrecan and a nonsignificant trend toward enhanced core binding factor alpha 1 (cbfa1), and collagen I. The expression of the osteoblast marker osterix and both lipoprotein receptor-related protein 6 and ␤-catenin, molecules of the wingless-type MMTV integration site family member (Wnt)/␤-catenin pathway induced during osteoblast differentiation, was suppressed. Conclusion-In the aorta of uremic rats, medial smooth muscle cells acquire a chondrocyte rather than osteoblast phenotype during the calcification process.

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“…Secondary antibody horseradish peroxidase-conjugated anti-rabbit IgG was from Sigma, and antimouse monoclonal antibody was from Pierce. Runx2 polyclonal antibody (type II-specific) was a kind gift from Dr. Narayanasamy Elango (25). AML1/ETO was a kind gift from Dr. Scott Hiebert (26), and pCMV5B(FLAG)Smurf1 plasmid was from Dr. Gerald Thomsen (27).…”

Section: Methodsmentioning

confidence: 99%

BMP-2 and Insulin-like Growth Factor-I Mediate Osterix (Osx) Expression in Human Mesenchymal Stem Cells via the MAPK and Protein Kinase D Signaling Pathways

Celil

Campbell

2005

Journal of Biological Chemistry

294

234

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Genetic studies place the transcription factor Osterix (Osx) downstream of Runx2, but limited information is available about Osx regulation during osteoblastic differentiation. An important role for bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-I (IGF-I) on Osx expression and the requirement for p38 for the BMP-2-mediated effect was reported previously by our group. In this study, we continued to investigate the molecular mechanisms by which BMP-2 and IGF-1 regulate Osx expression during osteoblast lineage progression. IGF-I-mediated Osx expression required all three MAPK components (Erk, p38, and JNK), whereas BMP-2 required p38 and JNK signaling. As a common mediator of growth factor signaling, we also investigated the involvement of protein kinase C/D (PKC/D) signaling. BMP-2-and IGF-I-mediated Osx expression was blocked in response to a PKD inhibitor. A selective inhibitor of conventional PKCs had no effect on the BMP-2-mediated Osx expression. BMP-2 and IGF-I induced a selective phosphorylation of PKD, and PKD was required for mineralization. PKC/D and MAPK signaling also mediate Runx2 activity. Therefore, to document the implication for Runx2 in Osx regulation, we blocked Runx2 activity using a dominant negative Runx2 construct and an ubiquitination mediator for Runx2 degradation. We showed that blocking Runx2 activity inhibited the BMP-2-mediated induction of Osx. These studies implicated that multiple signaling pathways mediate Osx, a critical gene for osteoblast differentiation and bone formation. In addition to Runx2, other signaling components may be necessary to regulate Osx during osteoblast lineage progression.

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Translational Regulation Is a Control Point in RUNX2/Cbfa1 Gene Expression

Cited by 54 publications

References 37 publications

MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures

MyoD enhances BMP7-induced osteogenic differentiation of myogenic cell cultures

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

BMP-2 and Insulin-like Growth Factor-I Mediate Osterix (Osx) Expression in Human Mesenchymal Stem Cells via the MAPK and Protein Kinase D Signaling Pathways

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