論文 - 詳細
| RRC ID | 45407 |
|---|---|
| 著者 | Bandow K, Kusuyama J, Kakimoto K, Ohnishi T, Matsuguchi T. |
| タイトル | AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation. |
| ジャーナル | Bone |
| Abstract |
Chondrocytes are derived from mesenchymal stem cells, and play an important role in cartilage formation. Sex determining region Y box (Sox) family transcription factors are essential for chondrogenic differentiation, whereas the intracellular signal pathways of Sox activation have not been clearly elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis. It is known that the catalytic alpha subunit of AMPK is activated by upstream AMPK kinases (AMPKKs) including liver kinase B1 (LKB1). We have previously reported that AMPK is a negative regulator of osteoblastic differentiation. Here, we have explored the role of AMPK in chondrogenic differentiation using in vitro culture models. The phosphorylation level of the catalytic AMPK alpha subunit significantly decreased during chondrogenic differentiation of primary chondrocyte precursors as well as ATDC-5, a well-characterized chondrogenic cell line. Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp). Thus, chondrocyte differentiation is functionally associated with decreased AMPK activity. |
| 巻・号 | 74 |
| ページ | 125-33 |
| 公開日 | 2015-5-1 |
| DOI | 10.1016/j.bone.2014.12.001 |
| PII | S8756-3282(14)00453-0 |
| PMID | 25497570 |
| MeSH | AMP-Activated Protein Kinases / metabolism* Aminoimidazole Carboxamide / analogs & derivatives Aminoimidazole Carboxamide / pharmacology Animals Base Sequence Cattle Cell Differentiation* / drug effects Cells, Cultured Chondrogenesis* / drug effects Embryo, Mammalian / cytology Embryo, Mammalian / drug effects Extremities / embryology Gene Knockdown Techniques Genes, Reporter Glucose / pharmacology Humans Luciferases / metabolism Metformin / pharmacology Mice, Inbred C57BL Molecular Sequence Data Phosphorylation / drug effects Protein Subunits / metabolism RNA, Small Interfering / metabolism Ribonucleotides / pharmacology SOX9 Transcription Factor / genetics SOX9 Transcription Factor / metabolism Sodium Selenite / pharmacology Stem Cells / cytology Stem Cells / drug effects Transcriptional Activation / drug effects Transcriptional Activation / genetics Transferrin / pharmacology |
| IF | 4.147 |
| 引用数 | 15 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |