AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation

Kenjiro Bandow, Joji Kusuyama, Kyoko Kakimoto, Tomokazu Ohnishi, Tetsuya Matsuguchi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalBone
Volume74
DOIs
Publication statusPublished - 2015 May 1
Externally publishedYes

Keywords

  • AMPK
  • Chondrocyte
  • Egr-1
  • Metformin
  • Sox9

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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