RRC ID 67963
Author Saita Y, Takagi T, Kitahara K, Usui M, Miyazono K, Ezura Y, Nakashima K, Kurosawa H, Ishii S, Noda M.
Title Lack of Schnurri-2 expression associates with reduced bone remodeling and osteopenia.
Journal J Biol Chem
Abstract Regulation of bone remodeling determines the levels of bone mass and its imbalance causes major skeletal diseases such as osteoporosis. A zinc finger protein, Schnurri-2 (SHN-2), was recently demonstrated to regulate bone morphogenetic protein-dependent adipogenesis and lymphogenesis. However, the role of SHN-2 in bone is not known. Here, we investigated the effects of Shn-2 deficiency on bone metabolism and cell function in Shn-2-null mice. Lack of SHN-2 expression reduced bone remodeling by suppressing both osteoblastic bone formation and osteoclastic bone resorption activities in vivo. Shn-2 deficiency suppressed osterix and osteocalcin expression as well as in vitro mineralization. Conversely, Shn-2 overexpression enhanced osteocalcin promoter activity and bone morphogenetic protein-dependent osteoblastic differentiation. Shn-2 deficiency suppressed Nfatc1 and c-fos expression leading to reduction of tartrate-resistant acid phosphatase-positive cell development in vivo as well as in the cultures of bone marrow cells. These studies demonstrate that SHN-2 regulates the activities of critical transcription factors required for normal bone remodeling.
Volume 282(17)
Pages 12907-15
Published 2007-4-27
DOI 10.1074/jbc.M611203200
PII S0021-9258(18)95066-0
PMID 17311925
MeSH Adipogenesis / genetics Animals Bone Marrow Cells / metabolism Bone Marrow Cells / pathology Bone Morphogenetic Proteins / biosynthesis Bone Resorption / genetics Bone Resorption / metabolism* Bone Resorption / pathology Cell Differentiation / genetics* Cells, Cultured DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / deficiency* Gene Expression Regulation / genetics* Male Mice Mice, Inbred BALB C Mice, Knockout NFATC Transcription Factors / biosynthesis Osteoblasts / metabolism Osteoblasts / pathology Osteocalcin / biosynthesis Osteoclasts / metabolism Osteoclasts / pathology Osteoporosis / genetics Osteoporosis / metabolism* Osteoporosis / pathology Proto-Oncogene Proteins c-fos / biosynthesis
IF 4.238
Human and Animal Cells MC3T3-E1(RCB1126)