title: Increased expression and activation of cathepsin K in human osteoarthritic cartilage and synovial tissues.
abstract: Few studies have analyzed Cathepsin K (CatK) expression in human osteoarthritic tissues. We investigated CatK expression and activation in human articular cartilage using clinical specimens. Human osteoarthritic cartilage was obtained during surgery of total hip arthroplasty (n = 10), and control cartilage was from that of femoral head replacement for femoral neck fracture (n = 10). CatB, CatK, CatL, CatS, and Cystatin C (CysC) expressions were evaluated immunohistochemically and by real-time PCR. Intracellular CatK protein was quantified by ELISA. Intracellular CatK activity was also investigated. Osteoarthritis (OA) chondrocytes were strongly stained with CatK, particularly in the superficial layer and more damaged areas. CatB, CatL, CatS, and CysC were weakly stained. CatK mRNA expression was significantly higher in OA group compared to that in control group (p = 0.043), whereas those of CatB, CatL, CatS, and CysC did not differ significantly. Mean CatK concentration (4.83 pmol/g protein) in OA chondrocytes was higher than that (3.91 pmol/g protein) in control chondrocytes (p = 0.001). CatK was enzymatically more activated in OA chondrocytes as compared with control chondrocytes. This study, for the first time, revealed increased CatK expression and activation in human OA cartilage, suggesting possible crucial roles for it in the pathogenesis of osteoarthritic change in articular cartilage.
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kozawa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urakawa
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Arai
authors.affiliation: Department of Orthopaedic Surgery, Nagoya Memorial Hospital, Nagoya, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Orthopaedic Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Orthopaedic Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kuzuya
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism*; D016022:Case-Control Studies; D056657:Cathepsin K / Q000378:metabolism*; D002478:Cells, Cultured; D055316:Cystatin C / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D055316:Cystatin C; D053583:Interleukin-1beta; D056657:Cathepsin K
keywords: Cathepsin K; articular cartilage; chondrocyte; osteoarthritis