Rheumatology: Current Research
Open Access
ISSN: 2161-1149 (Printed)
+44-20-4587-4809
ISSN: 2161-1149 (Printed)
+44-20-4587-4809
Martin Fuerst
Accepted Abstracts: Rheumatology & Orthopedics
In enchondral ossification, hypertrophic chondrocytes are specialized to remodel and mineralize the extracellular matrix (ECM). Chondrocyte hypertrophy occurs pathologically in OA and previous data suggest that the formation of different calcium crystals and their deposition in the cartilage matrix is part of the disease process. However, the exact mechanisms by which the formation of these crystals of their generation is linked to altered chrondocyte differentiation and to the pathogenesis of OA remain incompletely understood. Here, we sought to analyse systematically the prevalence and composition of calcium crystals in endstage knee OA of 120 patients as well as their relation to clinical disease score and histological changes. In addition, we investigated the expression of the different genes, known to be involved in matrix calcification, like ENPP1, ANK and TNAP in cultured chondrocytes of these patients and analyzed their potential to calcify ECM in vitro. We demonstrated mineralisation in cartilage specimens from all 120 patients. The size of calcified area showed a significant inverse correlation with the clinical knee score, and even more importantly a clear correlation also with the histological changes. FESEM analysis identified apatite or precursors of apatite minerals in all probes. All OA chondrocyte cultures showed a significant mineralisation capacity, while no mineralisation was seen with chondrocytes from healthy controls. In line with our in vivo findings, the minerals found in vitro were apatite or precursors of apatite, and no CPPD crystals were found. The extend of mineralisation of the cultures and the cartilage probes correlated with the expression of the hypertrophy marker collagen X. A differential regulation of the matrix calcification related gene ENPP1 was found. Our data demonstrate that mineralisation of articular cartilage is a regular event in end-stage OA that shows a strong correlation both with clinical symptoms and histological changes. As suggested by the nature of the crystals, the correlation to hypertrophy markes and in vitro calcification as well as the association with calcification related genes such as ENPP1, calcification of articular cartilage in OA is linked to mechanisms of enchondral ossification and may be an important part of the pathogenesis of the disease.