title: Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation and cartilage degradation in collagen antibody-induced arthritis in mice.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articular cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclasts and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be a promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicates the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reported that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA model mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation of articular cartilage in RA model mice.
  
  
  RESULTS
  We induced arthritis in mice by injection of anti-type II collagen antibodies and lipopolysaccharide (LPS). Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increased bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected with anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated with OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC1 did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articular cartilage from destruction in mice with arthritis.
  
  
  CONCLUSIONS
  Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammation in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. sfunato@dent.showa-u.ac.jp.|Department of Prosthodontics, Showa University School of Dentistry, Tokyo, Japan. sfunato@dent.showa-u.ac.jp.
authors.forename: Sakie
authors.initials: S
authors.lastname: Funato
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. aki_m168@med.showa-u.ac.jp.|Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan. aki_m168@med.showa-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsunaga
authors.affiliation: Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan. koei0525@med.showa-u.ac.jp.|Department of Orthopaedic Surgery, Showa University Northern Yokohama Hospital, Yokohama, Japan. koei0525@med.showa-u.ac.jp.
authors.forename: Koei
authors.initials: K
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. yoichim@dent.showa-u.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. kyoshimura@dent.showa-u.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Oral Diagnostic Sciences, Division of Pathology, Showa University School of Dentistry, Tokyo, Japan. jtanaka@dent.showa-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. dai.suzuki@dent.showa-u.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. uyama@dent.showa-u.ac.jp.
authors.forename: Risa
authors.initials: R
authors.lastname: Uyama
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. suzuki.hc@csp.or.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Oral Diagnostic Sciences, Division of Pathology, Showa University School of Dentistry, Tokyo, Japan. mishima-k@dent.showa-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Orthopaedic Surgery, Showa University Northern Yokohama Hospital, Yokohama, Japan. mas-nakamu@med.showa-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan. o-namiki@db3.sho-net.ne.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Namiki
authors.affiliation: Department of Prosthodontics, Showa University School of Dentistry, Tokyo, Japan. kazuyoshi@dent.showa-u.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Baba
authors.affiliation: Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan. katsu@med.showa-u.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Inagaki
authors.affiliation: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. kamijor@dent.showa-u.ac.jp.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D002356:Cartilage / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D053245:RANK Ligand / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D053245:RANK Ligand