Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage
- Equal contributors
1 Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, F-75205 Paris, France
2 INSERM, UMR-S606, hôpital Lariboisière, F-75475 Paris, France
3 CNRS-LCMCP-UPMC, Collège de France, 11 place M. Berthelot, 75231 Paris Cedex 05, France
4 Service des Explorations Fonctionnelles, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, 75020 Paris, France
5 Service de chirurgie orthopédique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Denis Diderot, Faculty of Medicine, 75010 Paris, France
6 Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS-Université de Lorraine, Faculté de medicine, Vandoeuvre Lès Nancy, 54505, France
7 DAL, Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, CH-1011, Lausanne, Switzerland
8 Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie, Centre Viggo Petersen, Pôle Appareil Locomoteur, 2 Rue Ambroise Paré, F-75010 Paris, France
Arthritis Research & Therapy 2013, 15:R103 doi:10.1186/ar4283Published: 3 September 2013
Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage.
We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients.
Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages.
CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.