Shoji Seki1, 2, Yoshiharu Kawaguchi2, Kazuhiro Chiba3, Yasuo Mikami4, Hideki Kizawa1, Takeshi Oya5, Futoshi Mio1, 3, Masaki Mori1, 4, Yoshinari Miyamoto1, Ikuko Masuda6, Tatsuhiko Tsunoda7, Michihiro Kamata3, 9, Toshikazu Kubo4, Yoshiaki Toyama3, Tomoatsu Kimura2, Yusuke Nakamura8
& Shiro Ikegawa11
Laboratory for Bone and Joint Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1 Shirokanedai, Minato-ku, Tokyo
108-8639, Japan.
2
Department of Orthopaedic Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama
930-0194, Japan.
3
Department of Orthopaedic Surgery, School of Medicine, Keio University, 35 Sinanomachi, Shinjuku-ku, Tokyo
160-8582, Japan.
4
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto
602-8566, Japan.
5
Second Department of Pathology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama
930-0194, Japan.
6
Division of Rheumatology, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin
53226, USA.
7
Laboratory for Medical Informatics, SNP Research Center, RIKEN, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama
230-0045, Japan.
8
Laboratory for Genotyping, SNP Research Center, RIKEN, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama
230-0045, Japan.
9
Present address: Department of Orthopedics, Keiyu Hospital, 3-7-3 Minatomirai, Yokohama
230-0012, Japan.
Correspondence should be addressed to Shiro Ikegawa sikegawa@ims.u-tokyo.ac.jp
C, resulting in the amino acid substitution I395T) in CILP, which encodes the cartilage intermediate layer protein, that acts as a modulator of LDD susceptibility. CILP was expressed abundantly in intervertebral discs, and its expression increased as disc degeneration progressed. CILP colocalized with TGF-
1 in clustering chondrocytes and their territorial matrices in intervertebral discs. CILP inhibited TGF-
