title: Potential involvement of SIRT1 in the pathogenesis of osteoarthritis through the modulation of chondrocyte gene expressions.
abstract: SIRT1 has been implicated as a key factor in aging-related diseases. Nevertheless, the role of SIRT1 in the pathogenesis of osteoarthritis (OA) is still unknown. We examined the expression of SIRT1 in cartilage samples and the effect of SIRT1 inhibition on chondrocyte gene expression changes to elucidate the role of SIRT1 in chondrocytes. SIRT1 expression was examined using cartilage samples from patients undergoing total knee arthroplasty and femoral head replacement by immunohistochemistry. The effect of SIRT1 inhibition by siRNA on chondrocyte gene expression was examined by real-time PCR and Western blotting. SIRT1 expression was barely detectable in the severely degenerated cartilage while SIRT1 was clearly expressed in the less damaged cartilage. The inhibition of SIRT1 by siRNA induced OA-like gene expression changes, namely the significant down-regulation of aggrecan and up-regulation of COL10A1 and ADAMTS-5. Our observations suggest that SIRT1 expression decreases with development of OA and the reduction of SIRT1 in chondrocytes may cause chondrocyte hypertrophy and cartilage matrix loss. SIRT1 might play important roles in the pathogenesis of OA.
authors.affiliation: Department of Orthopaedic Surgery; Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Fujita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Matsushita
authors.forename: Kazunari
authors.initials: K
authors.lastname: Ishida
authors.forename: Seiji
authors.initials: S
authors.lastname: Kubo
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Takayama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000368:Aged; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D019645:Arthroplasty, Replacement, Knee; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D005260:Female; D005270:Femur Head / Q000601:surgery; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D024121:Collagen Type X; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1