Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species

Abstract

Background 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. Methods 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). Results 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. Conclusion 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.

Dynamic weight-bearing test during jumping: A sensitive outcome measure of chronic osteoarthritis pain in rats

“…In the present study, a typical joint broadening symptom was observed after DMM surgery that peaked during week 1, persisted until the end of the study, and was sensitive to anti-inflammatory Zilretta treatment. Joint broadening can potentially be a consequence of surgery, synovitis, bone remodeling or another pathology [ 16 , 20 ]. The effect has been shown to be exaggerated when rats are housed in RCCs compared with type IV cages [ 15 ].…”

On-demand release of a selective MMP-13 blocker from an enzyme-responsive injectable hydrogel protects cartilage from degenerative progression in osteoarthritis

“…Journal of Materials Chemistry B mobility of the animals, with the outcome being similar to that observed in post-traumatic human OA. 61,[80][81][82][83] Studies have shown that the ACLT model exhibits changes in the cartilage and the underlying bone at the early stages of ligament transection. 62,81,82,84,85 The efficacy of the BI-4394 loaded hydrogel to prevent cartilage degradation through MMP-13 blocking was evaluated in an in vivo model.…”

“…61,[80][81][82][83] Studies have shown that the ACLT model exhibits changes in the cartilage and the underlying bone at the early stages of ligament transection. 62,81,82,84,85 The efficacy of the BI-4394 loaded hydrogel to prevent cartilage degradation through MMP-13 blocking was evaluated in an in vivo model. Post ACLT, the test animals were implanted with Gel@10 as a single dose (SD) or a double dose (DD) through IA administration, to determine the effective dose for therapeutic efficacy.…”