Zinc finger protein 521, a new player in bone formation.
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Zinc finger protein 521, a new player in bone formation. / Hesse, Eric; Kiviranta, Riku; Wu, Meilin; Saito, Hiroaki; Yamana, Kei; Correa, Diego; Atfi, Azeddine; Baron, Roland.
In: ANN NY ACAD SCI, Vol. 1192, 2010, p. 32-37.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Zinc finger protein 521, a new player in bone formation.
AU - Hesse, Eric
AU - Kiviranta, Riku
AU - Wu, Meilin
AU - Saito, Hiroaki
AU - Yamana, Kei
AU - Correa, Diego
AU - Atfi, Azeddine
AU - Baron, Roland
PY - 2010
Y1 - 2010
N2 - Exploration of anabolic pathways in osteoblasts revealed that Zfp521, a 30-zinc finger protein, is highly expressed at the periphery of mesenchymal condensations and in developing bones. In these structures it is expressed in chondroblasts, prehypertrophic chondrocytes, the periosteum, osteoblasts, osteoblast precursors, and osteocytes. Forced expression of Zfp521 in osteoblasts in vivo increases bone formation and bone mass, whereas preliminary data suggest that germline deletion leads to osteopenia. In contrast, overexpressing Zfp521 in vitro antagonizes, and knockdown favors, osteoblast differentiation and nodule formation. Zfp521 expression is inhibited by bone morphogenetic protein-2 and stimulated by parathyroid hormone-related protein. Mechanistically, Zfp521 binds to Runx2, repressing its transcriptional activity. These data support the hypothesis that Zfp521 both opposes the progression of precursors and promotes the maturation and function of mature osteoblasts. The balance between Zfp521 and Runx2 may therefore contribute to the regulation of osteoblast differentiation and bone formation.
AB - Exploration of anabolic pathways in osteoblasts revealed that Zfp521, a 30-zinc finger protein, is highly expressed at the periphery of mesenchymal condensations and in developing bones. In these structures it is expressed in chondroblasts, prehypertrophic chondrocytes, the periosteum, osteoblasts, osteoblast precursors, and osteocytes. Forced expression of Zfp521 in osteoblasts in vivo increases bone formation and bone mass, whereas preliminary data suggest that germline deletion leads to osteopenia. In contrast, overexpressing Zfp521 in vitro antagonizes, and knockdown favors, osteoblast differentiation and nodule formation. Zfp521 expression is inhibited by bone morphogenetic protein-2 and stimulated by parathyroid hormone-related protein. Mechanistically, Zfp521 binds to Runx2, repressing its transcriptional activity. These data support the hypothesis that Zfp521 both opposes the progression of precursors and promotes the maturation and function of mature osteoblasts. The balance between Zfp521 and Runx2 may therefore contribute to the regulation of osteoblast differentiation and bone formation.
KW - Animals
KW - Humans
KW - Models, Biological
KW - Transcription, Genetic
KW - Cell Differentiation/genetics/physiology
KW - Chondrocytes/metabolism/physiology
KW - Core Binding Factor Alpha 1 Subunit/genetics/metabolism/physiology
KW - DNA-Binding Proteins/genetics/metabolism/physiology
KW - Osteoblasts/metabolism/physiology
KW - Osteogenesis/genetics/physiology
KW - Animals
KW - Humans
KW - Models, Biological
KW - Transcription, Genetic
KW - Cell Differentiation/genetics/physiology
KW - Chondrocytes/metabolism/physiology
KW - Core Binding Factor Alpha 1 Subunit/genetics/metabolism/physiology
KW - DNA-Binding Proteins/genetics/metabolism/physiology
KW - Osteoblasts/metabolism/physiology
KW - Osteogenesis/genetics/physiology
M3 - SCORING: Journal article
VL - 1192
SP - 32
EP - 37
JO - ANN NY ACAD SCI
JF - ANN NY ACAD SCI
SN - 0077-8923
ER -
