Unraveling the Mechanisms of Hypertrophy-Induced Matrix Mineralization and Modifications in Articular Chondrocytes.

Chondrocyte hypertrophic differentiation is a main event leading to articular cartilage degradation in osteoarthritis. It is associated with matrix remodeling and mineralization, the dynamics of which is not well characterized during chondrocyte hypertrophic differentiation in articular cartilage. Based on an in vitro model of progressive differentiation of immature murine articular chondrocytes (iMACs) into prehypertrophic (Prehyp) and hypertrophic (Hyp) chondrocytes, we performed kinetics of chondrocyte differentiation from Prehyp to Hyp to follow matrix mineralization and remodeling by immunofluorescence, biochemical, molecular, and physicochemical approaches, including atomic force microscopy, scanning electron microscopy associated with energy-dispersive X-ray spectroscopy (SEM-EDS), attenuated total reflection infrared analyses, and X-ray diffraction.

Deciphering pathological remodelling of the human cartilage extracellular matrix in osteoarthritis at the supramolecular level.

The extracellular matrix (ECM) of articular cartilage is a three-dimensional network mainly constituted of entangled collagen fibrils and interfibrillar aggrecan aggregates. During the development of osteoarthritis (OA), the most common musculoskeletal disorder, the ECM is subjected to a combination of chemical and structural changes that play a pivotal role in the initiation and the progress of the disease. While the molecular mechanisms involved in the pathological remodelling of the ECM are considered as decisive, they remain, however, not completely elucidated.