CITED2 mediates the mechanical loading–induced suppression of adipokines in the infrapatellar fat pad

Lidi Liu, Zhiyong He, Lin Xu, Laijin Lu, Haotian Feng, Daniel J. Leong, Sun J. Kim, David M. Hirsh, Robert J. Majeska, Mary B. Goldring, Neil J. Cobelli, Hui B. Sun

Research output: Contribution to journalArticle

Abstract

Adipokines secreted from the infrapatellar fat pad (IPFP), such as adipsin and adiponectin, have been implicated in osteoarthritis pathogenesis. CITED2, a mechanosensitive transcriptional regulator with chondroprotective activity, may modulate their expression. Cited2 haploinsufficient mice (Cited2+/−) on a high-fat diet (HFD) exhibited increased body weight and increased IPFP area compared to wild-type (WT) mice on an HFD. While an exercise regimen of moderate treadmill running induced the expression of CITED2, as well as PGC-1α, and reduced the expression of adipsin and adiponectin in the IPFP of WT mice on an HFD, Cited2 haploinsufficiency abolished the loading-induced expression of PGC-1α and loading-induced suppression of adipsin and adiponectin. Furthermore, knocking down or knocking out CITED2 in adipose stem cells (ASCs)/preadipocytes derived from the IPFP in vitro led to the increased expression of adipsin and adiponectin and reduced PGC-1α, and abolished the loading-induced suppression of adipsin and adiponectin and loading-induced expression of PGC-1α. Overexpression of PGC-1α in these ASC/preadipocytes reversed the effects caused by CITED2 deficiency. The current data suggest that CITED2 is a critical regulator in physiologic loading-induced chondroprotection in the context of an HFD and PGC-1α is required for the inhibitory effects of CITED2 on the expression of adipokines such as adipsin and adiponectin in the IPFP.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1442
Issue number1
DOIs
StatePublished - Apr 2019

Keywords

  • CITED2
  • PGC-1α
  • adiponectin
  • adipsin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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