title: AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation.
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.
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Bandow
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kusuyama
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kakimoto
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. Electronic address: tmatsugu@dent.kagoshima-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D005121:Extremities / Q000196:embryology; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014168:Transferrin / Q000494:pharmacology
chemical_list: D021122:Protein Subunits; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D055758:SOX9 Transcription Factor; D014168:Transferrin; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D008156:Luciferases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D018038:Sodium Selenite; D005947:Glucose
keywords: AMPK; Chondrocyte; Egr-1; Metformin; Sox9