Protein modification by deamidation indicates variations in joint extracellular matrix turnover.

Area of Science:

• Biochemistry
• Biomarkers
• Extracellular Matrix Biology

Background:

• Extracellular proteins accumulate unrepaired post-translational modifications with age.
• These modifications may serve as biomarkers for chronic arthritic diseases like osteoarthritis (OA).

Purpose of the Study:

• To investigate deamidated COMP (D-COMP) as a systemic biomarker for OA.
• To assess the specificity of D-COMP for joint site and OA severity.

Main Methods:

• Predicted deamidation sites in cartilage oligomeric matrix protein (COMP).
• Confirmed deamidated COMP (Asp(64)) and native COMP (Asn(64)) in cartilage via mass spectrometry.
• Developed a D-COMP-specific ELISA using a novel monoclonal antibody.
• Analyzed serum D-COMP and total COMP in joint replacement patients and 450 OA participants.

Main Results:

• Deamidated COMP (D-COMP) was detected in cartilage and systemic circulation.
• Serum D-COMP levels decreased post-joint replacement, indicating a joint tissue source.
• D-COMP associated with radiographic hip OA severity (p < 0.0001), while total COMP associated with knee OA severity (p < 0.0001).
• D-COMP was enriched in hip OA cartilage near lesions compared to remote or knee OA cartilage.

Conclusions:

• D-COMP is present in articular cartilage and circulation, serving as the first joint site-specific OA biomarker.
• Enrichment of D-COMP in hip OA cartilage suggests a diminished repair response compared to knee OA.
• D-COMP shows potential for monitoring hip OA progression and understanding disease mechanisms.