Lack of Schnurri-2 expression associates with reduced bone remodeling and osteopenia.
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.
Saita
Yoshitomo
Y
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Takagi
Tsuyoshi
T
Kitahara
Keiichiro
K
Usui
Michihiko
M
Miyazono
Kohei
K
Ezura
Yoichi
Y
Nakashima
Kazuhisa
K
Kurosawa
Hisashi
H
Ishii
Shunsuke
S
Noda
Masaki
M
D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency*; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000096:biosynthesis; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D015675:Osteocalcin