Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species
Gigout A., Harazin D., Topping LM., Merciris D., Lindemann S., Brenneis C., Nissim A.
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Inflammatory mediators, proteases, and oxidants produced by chondrocytes are known to be responsible for driving cartilage degradation. Nevertheless, the early pathogenic events are still unclear. To investigate this, we employed an antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed after 3, 5, 7, 14, and 28 days. Alternatively, anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) was performed and animals were sacrificed after 1, 3, 5, 7, and 14 days. Joints were stained with toluidine blue and saffron du Gatinais for histological scoring, anti-oxPTM-CII, and anti-collagen type X antibodies (anti-CX).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We observed positive oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries, respectively, before overt cartilage lesions were visible. oxPTM-CII was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes, and co-localized with CX staining. Staining was weak or absent for the lateral compartment or the contralateral knees except at later time points.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The results demonstrate that oxidant production and chondrocyte hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead of radiographic changes.</jats:p> </jats:sec>