| RRC ID |
41819
|
| 著者 |
Duarte WR, Shibata T, Takenaga K, Takahashi E, Kubota K, Ohya K, Ishikawa I, Yamauchi M, Kasugai S.
|
| タイトル |
S100A4: a novel negative regulator of mineralization and osteoblast differentiation.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
S100A4 is an intracellular calcium-binding protein expressed by osteoblastic cells. However, its roles in bone physiology are unknown. Because before matrix mineralization, its expression is markedly diminished, we hypothesized that S100A4 negatively regulates the mineralization process. In this study, we investigated the effects of the inhibition of S100A4 synthesis on osteoblast differentiation and in vitro mineralized nodule formation. Inhibition of S100A4 synthesis was achieved by an antisense approach in the mouse osteoblastic cell line MC3T3-E1. Cell clones that synthesized low levels of S100A4 (AS clones) produced markedly increased number of mineralized nodules at much earlier stages in comparison with controls as demonstrated by Alizarin red S and von Kossa staining. The expression of type I collagen (COLI) and osteopontin (OPN) increased in AS clones compared with controls. Bone sialoprotein (BSP) and osteocalcin (OCN), molecules associated with mineralization and markers for mature osteoblastic phenotype, were expressed in AS clones before their detection in controls. Because S100A4 was not localized in the nucleus of MC3T3-E1 cells and AS clones, it is unlikely that S100A4 directly regulates the expression of these genes. Moreover, the expression of Cbfal/Osf-2 and Osx, transcription factors necessary for the expression of osteoblast-associated genes, remained unchanged in AS clones, indicating that S100A4 may be downstream to these transcription factors. These findings indicate that S100A4 is a novel negative regulator of matrix mineralization likely by modulating the process of osteoblast differentiation.
|
| 巻・号 |
18(3)
|
| ページ |
493-501
|
| 公開日 |
2003-3-1
|
| DOI |
10.1359/jbmr.2003.18.3.493
|
| PMID |
12619934
|
| MeSH |
3T3 Cells
Animals
Base Sequence
Biomarkers
Blotting, Western
Calcification, Physiologic / physiology*
Cell Differentiation / physiology*
DNA Primers
Fluorescent Antibody Technique
Mice
Osteoblasts / cytology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
S100 Calcium-Binding Protein A4
S100 Proteins / genetics
S100 Proteins / physiology*
|
| IF |
5.854
|
| 引用数 |
67
|
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
