論文 - 詳細
| RRC ID | 18168 |
|---|---|
| 著者 | Chen W, Zhang X, Siu RK, Chen F, Shen J, Zara JN, Culiat CT, Tetradis S, Ting K, Soo C. |
| タイトル | Nfatc2 is a primary response gene of Nell-1 regulating chondrogenesis in ATDC5 cells. |
| ジャーナル | J Bone Miner Res |
| Abstract |
Nell-1 is a growth factor required for normal skeletal development and expression of extracellular matrix proteins required for bone and cartilage cell differentiation. We identified the transcription factor nuclear factor of activated T cells (Nfatc2) as a primary response gene of Nell-1 through a microarray screen, with validation using real-time polymerase chain reaction (PCR). We investigated the effects of recombinant Nell-1 protein on the chondrogenic cell line ATDC5 and primary mouse chondrocytes. The osteochondral transcription factor Runx2 was investigated as a possible intermediary between Nell-1 and Nfatc2 using adenoviral overexpression of wild-type and dominant-negative Runx2. Nell-1 transiently induced both transcription and translation of Nfatc2, an effect inhibited by transduction of dominant-negative Runx2, suggesting that Runx2 was necessary for Nfatc2 induction. Differentiation assays revealed inhibitory effects of Nell-1 on ATDC5 cells. Although proliferation was unaffected, expression of chondrocyte-specific genes was decreased, and cartilage nodule formation and proteoglycan accumulation were suppressed. siRNA knockdown of Nfatc2 significantly reversed these inhibitory effects. To elucidate the relationship between Nell-1, Runx2, and Nfatc2 in vivo, their presence and distribution were visualized in femurs of wild-type and Nell1-deficient mice at both neonatal and various developmental stages using immunohistochemistry. All three proteins colocalized in the perichondrium of wild-type femurs but stained weakly or were completely absent in Nell1-deficient femurs at neonatal stages. Thus Nfatc2 likely plays an important role in Nell-1-mediated osteochondral differentiation in vitro and in vivo. To our knowledge, this is the first demonstration that Nfatc2 is a primary response gene of Nell-1. |
| 巻・号 | 26(6) |
| ページ | 1230-41 |
| 公開日 | 2011-6-1 |
| DOI | 10.1002/jbmr.314 |
| PMID | 21611965 |
| PMC | PMC3312756 |
| MeSH | Animals Calcium-Binding Proteins / deficiency Calcium-Binding Proteins / metabolism* Cell Differentiation / drug effects Cell Line Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / drug effects Chondrogenesis / genetics* Core Binding Factor Alpha 1 Subunit / metabolism Femur / cytology Femur / drug effects Femur / metabolism Gene Expression Regulation / drug effects Glycoproteins / deficiency Glycoproteins / metabolism* Humans Immunohistochemistry Mice NFATC Transcription Factors / genetics* Nerve Tissue Proteins / pharmacology Oligonucleotide Array Sequence Analysis Protein Biosynthesis / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / metabolism Reproducibility of Results Reverse Transcriptase Polymerase Chain Reaction Time Factors |
| IF | 5.854 |
| 引用数 | 22 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |