Details

Autor(en) / Beteiligte

• Ikegawa, Shiro
• Seki, Shoji
• Kawaguchi, Yoshiharu
• Chiba, Kazuhiro
• Mikami, Yasuo
• Kizawa, Hideki
• Oya, Takeshi
• Mio, Futoshi
• Mori, Masaki
• Miyamoto, Yoshinari
• Masuda, Ikuko
• Tsunoda, Tatsuhiko
• Kamata, Michihiro
• Kubo, Toshikazu
• Toyama, Yoshiaki
• Kimura, Tomoatsu
• Nakamura, Yusuke

Titel

A functional SNP in CILP , encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease

Ist Teil von

• Nature genetics, 2005-06, Vol.37 (6), p.607-612

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Lumbar disc disease (LDD) is caused by degeneration of intervertebral discs of the lumbar spine. One of the most common musculoskeletal disorders, LDD has strong genetic determinants. Using a case-control association study, we identified a functional SNP (1184T → 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-β1 in clustering chondrocytes and their territorial matrices in intervertebral discs. CILP inhibited TGF-β1-mediated induction of cartilage matrix genes through direct interaction with TGF-β1 and inhibition of TGF-β1 signaling. The susceptibility-associated 1184C allele showed increased binding and inhibition of TGF-β1. Therefore, we conclude that the extracellular matrix protein CILP regulates TGF-β signaling and that this regulation has a crucial role in the etiology and pathogenesis of LDD. Our study also adds to the list of connective tissue diseases that are associated with TGF-β.