Intra-Articular Cartilage Calcification Associated with Type II Pro-Collagen Accumulation in Chondrocytes and Abnormal Fibrils in the Extra Cellular Matrix (ECM): Case Report

Abstract

Objective: The purpose of this case-study was to perform morphological and molecular analysis of articular cartilage biopsies from the femoral condyle of a 33 year old woman with intra-articular calcification in the right knee joint and compare the findings with those of normal cartilage. Methods: Femural condyle cartilage biopsies were used for Light Microscopy (LM), Transmission Electron Microscopy (TEM), explant culturing and DNA mutation analysis of the COL2A1 gene. Results: X-ray of the affected knee joint showed intra-articular calcifications on the femur condyle, tibia and meniscus. Pathological LM and TEM examination of cartilage biopsies revealed calcified islands morphologically identical to calcium pyro-phosphate dehydrate (CPPD) and hydroxyapatite (HA)-like crystals. In addition, chondrocytes showed accumulation of pro-collagen molecules. With explant culturing and immunochemistry, it was confirmed that matrix calcification correlated with high intracellular matrix accumulation and expression of type X collagen. The induction of hypertrophy in chondrocytes was further associated with matrix vesicle (MV) release and a prominent calcification zone. Surprisingly, TEM showed crystal development on thick abnormal type II collagen fibrils suggesting that these ECM components might nucleate and contribute to calcification. Conclusions: We suggest that intra-articular calcification may be associated with type II pro-collagen accumulation in chondrocytes. In particular, we hypothesize that matrix accumulation may induce hypertrophy and type X collagen expression in cartilage cells and release of MV’s into the ECM, which together with thick abnormal type II collagen hetero-fibrils, are responsible for crystal deposition in the ECM.