Bone Morphogenetic Protein 2 Induces Cyclo-oxygenase 2 in Osteoblasts via a Cbfa1 Binding Site: Role in Effects of Bone Morphogenetic Protein 2 In Vitro and In Vivo

Chikazu, Daichi; Li, Xiaodong; Kawaguchi, Hiroshi; Sakuma, Yoshiharu; Voznesensky, Olga; Adams, Douglas; Xu, Manshan; Hoshi, Kazuto; Katavić, Vedran; Herschman, Harvey R.; Raisz, Lawrence G.; Pilbeam, Carol C.

doi:10.1359/jbmr.2002.17.8.1430

Cited by 103 publications

(73 citation statements)

References 51 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other laboratories also demonstrate that mutations of Runx2 binding sites in type X collagen and COX-2 promoters inhibit effects of BMP-2 on activation of these promoters (15,30). These findings demonstrate that interaction of Smad1 with Runx2 at the OSE2 site may be the major mechanism for BMP-2 to activate its downstream target genes in bone cells.…”

Section: Discussionmentioning

confidence: 75%

Bone Morphogenetic Protein 2 Activates Smad6 Gene Transcription through Bone-specific Transcription Factor Runx2

Wang

Wei

Zhu

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 75%

Bone Morphogenetic Protein 2 Activates Smad6 Gene Transcription through Bone-specific Transcription Factor Runx2

Wang

Wei

Zhu

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In the present studies, we found that Cbfa1 is required to activate BMP-2 signaling. It has been reported (18,19) that Smad1 and Cbfa1 binding sites co-localize in the promoters of several bone-related genes. Taken together with our results, this suggests that Smad1 and Cbfa1 co-activate downstream target genes in osteoblasts.…”

Section: Figmentioning

confidence: 99%

E3 Ubiquitin Ligase Smurf1 Mediates Core-binding Factor α1/Runx2 Degradation and Plays A Specific Role in Osteoblast Differentiation

Zhao

Qiao

Oyajobi

et al. 2003

Journal of Biological Chemistry

254

263

View full text Add to dashboard Cite

Osteoblast differentiation and bone formation is stimulated by bone morphogenetic protein (BMP)-2 and its downstream signaling molecules Smad1 and -5 and the osteoblast-specific transcription factor core-binding factor ␣1 (Cbfa1). Proteolytic degradation of Smad1 and Cbfa1 is proteasome-dependent, and intracellular concentrations of Smad1 and Cbfa1 are enhanced by inhibition of the 26 S proteasome. Smad1 degradation is mediated by the E3 ubiquitin ligase Smurf1 (Smad ubiquitin regulatory factor 1), but the specific E3 ligase responsible for Cbfa1 degradation has not been identified. Because Cbfa1 interacts with Smad1, whose degradation is mediated by Smurf1, we examined the effect of Smurf1 on Cbfa1 degradation in osteoblast precursor cells. Smurf1 interacts directly with Cbfa1 and mediates Cbfa1 degradation in a ubiquitin-and proteasome-dependent manner. Because Smurf1 controls the intracellular concentrations of several key molecules in the bone formation cascade, we examined the effect of a mutant form of Smurf1 in osteoblasts and found that expression of mutant Smurf1 markedly enhanced osteoblast differentiation. Smurf1 therefore appears to be an important regulatory factor in osteoblast differentiation and a potential molecular target for identification of bone anabolic agents.

show abstract

“…PASMC from patients with FPPH exhibited abnormal growth responses to BMP treatment, suggesting that normal BMP signaling through wild-type BMPR2 may regulate cell growth. In addition, BMP treatment of osteoblasts has recently been reported to induce cyclooxygenase-2 transcription [28].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells

Caldwell¹,

Gadipatti

Lane

et al. 2005

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The bone morphogenetic protein receptor-2 (BMPR2) is a member of the transforming growth factor-beta receptor family and is expressed on the surface of several cell types including endothelial cells and macrophages. Recently, a cause for familial primary pulmonary hypertension (FPPH) has been identified as mutations in the gene encoding BMPR2. Three forms of pulmonary hypertension (PH) exist, including PPH, FPPH, and PH secondary to other etiologies (sporadic PH) such as drug abuse and human immunodeficiency virus (HIV) infection. It is interesting that these subtypes are histologically indistinguishable. The macrophage is a key target cell for HIV-1, significantly altering macrophage cell function upon infection. HIV-1 trans-activator of transcription (Tat), an immediate-early product of the HIV-1 lifecycle, plays an important role in mediating HIV-induced modulation of host cell function. Our laboratory has previously shown that Tat represses mannose receptor transcription in macrophages. In the current study, we examined activity from the BMPR2 promoter in the macrophage cell line U937 and potential regulation by Tat. Transfection of U937 cells with BMPR2 promoter-reporter constructs revealed dose-dependent repression of BMPR2 promoter activity in the presence of Tat. Experiments using truncations of the BMPR2 promoter localized Tat-mediated repression to the first 208 bases of the promoter. Decreased BMPR2 transcription resulted in altered downstream signaling. Similar to mothers against decapentaplegics (SMAD) phosphorylation and SMAD6 expression, in response to BMP2 treatment, were down-regulated after Tat treatment. Finally, HIV-1 infection and treatment with Tat protein of the U937 human monocytic cell line resulted in a decreased, endogenous BMPR2 transcript copy number.

show abstract

Bone Morphogenetic Protein 2 Induces Cyclo-oxygenase 2 in Osteoblasts via a Cbfa1 Binding Site: Role in Effects of Bone Morphogenetic Protein 2 In Vitro and In Vivo

Cited by 103 publications

References 51 publications

Bone Morphogenetic Protein 2 Activates Smad6 Gene Transcription through Bone-specific Transcription Factor Runx2

Bone Morphogenetic Protein 2 Activates Smad6 Gene Transcription through Bone-specific Transcription Factor Runx2

E3 Ubiquitin Ligase Smurf1 Mediates Core-binding Factor α1/Runx2 Degradation and Plays A Specific Role in Osteoblast Differentiation

HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells

Contact Info

Product

Resources

About