ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein

Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-06, Vol.281 (23), p.15800-15808
Main Authors: Liu, Chuan-ju, Kong, Wei, Xu, Ke, Luan, Yi, Ilalov, Kiril, Sehgal, Bantoo, Yu, Shuang, Howell, Ronald D., Di Cesare, Paul E.
Format: Article
Language:English
Subjects:
ADAM Proteins - metabolism
ADAMTS Proteins
Bone and Bones - metabolism
Cartilage Oligomeric Matrix Protein
Extracellular Matrix Proteins - metabolism
Glycoproteins - metabolism
Humans
Hydrolysis
Immunoprecipitation
Matrilin Proteins
Polymerase Chain Reaction
Protein Binding
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Summary:Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (adisintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factor-like repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn2+ and appropriate pH (7.5–9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M513433200