title: Involvement of ERCC1 in the pathogenesis of osteoarthritis through the modulation of apoptosis and cellular senescence.
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 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. 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)
authors: Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219; Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213.
authors: Koji
authors: K
authors: Takayama
authors: Yohei
authors: Y
authors: Kawakami
authors: Sahnghoon
authors: S
authors: Lee
authors: Nick
authors: N
authors: Greco
authors: Mitra
authors: M
authors: Lavasani
authors: Yutaka
authors: Y
authors: Mifune
authors: James H
authors: JH
authors: Cummins
authors: Takashi
authors: T
authors: Yurube
authors: Ryosuke
authors: R
authors: Kuroda
authors: Masahiro
authors: M
authors: Kurosaka
authors: Freddie H
authors: FH
authors: Fu
authors: Johnny
authors: J
authors: Huard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002358:Cartilage, Articular / Q000502:physiology / Q000503:physiopathology; D016922:Cellular Senescence / Q000235:genetics; D019902:Chondrocytes / Q000473:pathology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004720:Endonucleases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; C499360:Ercc1 protein, mouse
keywords: ERCC1; apoptosis; interleukin (IL)-1β; osteoarthritis; senescence