Involvement of ERCC1 in the pathogenesis of osteoarthritis through the modulation of apoptosis and cellular senescence

Koji Takayama, Yohei Kawakami, Sahnghoon Lee, Nick Greco, Mitra Lavasani, Yutaka Mifune, James H. Cummins, Takashi Yurube, Ryosuke Kuroda, Masahiro Kurosaka, Freddie H. Fu, Johnny Huard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4h of exposure to interleukin (IL)-1β, but decreased after 12h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment. (191)

Original languageEnglish (US)
Pages (from-to)1326-1332
Number of pages7
JournalJournal of Orthopaedic Research
Volume32
Issue number10
DOIs
StatePublished - Oct 2014

Keywords

  • ERCC1
  • apoptosis
  • interleukin (IL)-1β
  • osteoarthritis
  • senescence

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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