title: Joint Degradation in a Monkey Model of Collagen-Induced Arthritis: Role of Cathepsin K Based on Biochemical Markers and Histological Evaluation.
abstract: The role of cathepsin K in joint degradation in a model of collagen-induced arthritis (CIA) in cynomolgus monkey was examined using biochemical markers and histology. Joint swelling, urinary C-telopeptide of type II collagen (CTX-II), deoxypyridinoline (DPD), and N- and C-telopeptides of type I collagen (NTX and CTX-I, resp.) were analyzed. Immunohistochemistry of type II collagen, cathepsin K, and CTX-II were performed using joints. Joint swelling reached peak on day 42 and continued at this level. The CTX-II level peaked on day 28 and declined thereafter, while CTX-I, NTX, and DPD reached plateau on day 43. Joint swelling was positively correlated with CTX-II increases on days 20 and 42/43, with increases in CTX-I and NTX/Cr on days 42/43 and 84, and with DPD increases throughout the study period. Intense cathepsin K staining was observed in osteoclasts and in articular cartilage and synovial tissue in arthritic joints. CTX-II was present in the superficial layer of articular cartilage in CIA monkeys. Evidence from biochemical markers suggests that matrix degradation in the CIA model starts with degradation of cartilage, rather than bone resorption. Cathepsin K expressed in osteoclasts, articular cartilage, and synovial tissue may contribute to degradation of cartilage.
authors.affiliation: Research Promotion, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.affiliation: Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ochi
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories, Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Horai
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan; Shandong Provincial Key Laboratory of Oral Biomedicine, The School of Stomatology, Shandong University, Jinan 250012, China.
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka