Conditional deletion of gremlin causes a transient increase in bone formation and bone mass.

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Abstract Text:

Elisabetta Gazzerro,Anna Smerdel-Ramoya,Stefano Zanotti,Lisa Stadmeyer,Deena Durant,Aris N Economides,Ernesto Canalis,Elisabetta Gazzerro,Anna Smerdel-Ramoya,Stefano Zanotti,Lisa Stadmeyer,Deena Durant,Aris N Economides,Ernesto Canalis,

Gremlin is a glycoprotein that binds bone morphogenetic proteins (BMPs) 2, 4, and 7, antagonizing their actions. Gremlin opposes BMP effects on osteoblastic differentiation and function in vitro and in vivo, and its overexpression causes osteopenia. To define the function of gremlin in the skeleton, we generated gremlin 1 (grem1) conditional null mice by mating mice where grem1 was flanked by lox(P) sequences with mice expressing the Cre recombinase under the control of the osteocalcin promoter. grem1 null male mice displayed increased trabecular bone volume due to enhanced osteoblastic activity, because mineral apposition and bone formation rates were increased. Osteoblast number and bone resorption were not altered. Marrow stromal cells from grem1 conditional null mice expressed higher levels of alkaline phosphatase activity. Gremlin down-regulation by RNA interference in ST-2 stromal and MC3T3 osteoblastic cells increased the BMP-2 stimulatory effect on alkaline phosphatase activity, on Smad 1/5/8 phosphorylation, and on the transactivation of the BMP/Smad reporter construct 12xSBE-Oc-pGL3. Gremlin down-regulation also enhanced osteocalcin and Runx-2 expression, Wnt 3a signaling, and activity in ST-2 cells. In conclusion, deletion of grem1 in the bone microenvironment results in sensitization of BMP signaling and activity and enhanced bone formation in vivo.

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Publishing Authors By Initials

E Gazzerro,A Smerdel-Ramoya,S Zanotti,L Stadmeyer,D Durant,AN Economides,E Canalis,E Gazzerro,A Smerdel-Ramoya,S Zanotti,L Stadmeyer,D Durant,AN Economides,E Canalis,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 31549-57

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 4

MONTH: 09

YEAR: 2007

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Conditional deletion of gremlin causes a transient increase in bone formation and bone mass. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Conditional deletion of gremlin causes a transient increase in bone formation and bone mass.

AFFILIATION: Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: AR21707

ACRONYM: AR

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Conditional deletion of gremlin causes a transient increase in bone formation and bone mass Related Publications

• Activation of the ERK pathway in osteoblastic cells, role of gremlin and BMP-2.
• Bone morphogenetic protein-2 suppresses collagenase-3 promoter activity in osteoblasts through a runt domain factor 2 binding site.
• Bone morphogenetic proteins induce gremlin, a protein that limits their activity in osteoblasts.
• CCAAT/Enhancer-binding protein homologous protein (CHOP) decreases bone formation and causes osteopenia.
• CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation.
• Conditional deletion of gremlin causes a transient increase in bone formation and bone mass.
• Connective tissue growth factor enhances osteoblastogenesis in vitro.
• Effect of growth factors on bone cell replication and differentiation.
• Effects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression.
• Expression and regulation of CCN genes in murine osteoblasts.
• Gene delivery by retroviruses.
• Growth hormone, insulin-like growth factors, and the skeleton.
• Local bone growth factors.
• Nephroblastoma overexpressed (Nov) inhibits osteoblastogenesis and causes osteopenia.
• Nephroblastoma overexpressed (nov) is a novel bone morphogenetic protein antagonist.
• Notch inhibits osteoblast differentiation and causes osteopenia.
• Notch signaling in osteoblasts.
• Regulation of collagenase-3 by bone morphogenetic protein-2 in bone cell cultures.
• Skeletal overexpression of connective tissue growth factor impairs bone formation and causes osteopenia.
• Transcriptional regulation of connective tissue growth factor by cortisol in osteoblasts.
• Transient focal lesion in the splenium of the corpus callosum: MR imaging with an attempt to clinical-physiopathological explanation and review of the literature.
• Twisted gastrulation, a bone morphogenetic protein agonist/antagonist, is not required for post-natal skeletal function.