期刊
BONE
卷 44, 期 4, 页码 528-536出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2008.11.011
关键词
Zfp521; Runx2; Osteoblast; Bone formation; Differentiation
资金
- National Institutes of Health [AR48218, DE12616]
- Yale Core Center for Musculoskeletal Diseases [AR46032]
- Deutsche Forschungsgememschaft [HE 5208/1-1]
- International Bone and Mineral Society Gideon and Sevgi Rodan Fellowship
- Gustavus and Louise Pfeiffer Research Foundation's George Robert Pfeiffer Fellowship
- UNCF-Merck Dissertation Fellowship
- Academy of Finland
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR048218, P30AR046032, R01AR057769] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R01DE012616] Funding Source: NIH RePORTER
Zfp521, a 30 C2H2 Kruppel-like zinc finger protein, is expressed at high levels at the periphery of early mesenchymal condensations prefiguring skeletal elements and in all developing bones in the perichondrium and periosteum, in osteoblast precursors and osteocytes, and in chondroblast precursors and growth plate prehypertrophic chondrocytes. Zfp521 expression in cultured mesenchymal cells is decreased by BMP-2 and increased by PTHrP, which promote and antagonize osteoblast differentiation, respectively. In vitro, Zfp521 overexpression reduces the expression of several downstream osteoblast marker genes and antagonizes osteoblast differentiation. Zfp521 binds Runx2 and represses its transcriptional activity, and Runx2 dose-dependently rescues Zfp521's inhibition of osteoblast differentiation. In contrast, osteocalcin promoter-targeted overexpression of Zfp521 in osteoblasts in vivo results in increased bone formation and bone mass, We propose that Zfp521 regulates the rate of osteoblast differentiation and bone formation during development and in the mature skeleton, in part by antagonizing Runx2. (C) 2008 Elsevier Inc. All rights reserved.
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