Artikel
BCP and CPPD crystalopathies exhibit distinct effects on the chondrocyte phenotype
Suche in Medline nach
Autoren
Veröffentlicht: | 8. Oktober 2019 |
---|
Gliederung
Text
Background: Calcification of cartilage with BCP crystals is a common finding during osteoarthritis (OA) and is directly linked to the severity of the disease and hypertrophic differentiation of chondrocytes. In some OA cartilage samples calcium pyrophosphate dihydrate (CPPD) crystals can be found. The mechanism underlying the formation of the CPPD crystals and their effects on the chondrocytes are not completely understood. The aim of this study was to evaluate the effect of CPPD compared to BCP crystals on the chondrocyte phenotype in OA cartilage.
Methods: Cartilage samples of patients with chondrocalcinosis (CC) were used and compared with samples of severe OA patients without CC and healthy cartilage samples served as control. Radiological presence of CC was evaluated using standard X-ray pictures, as well as macroscopically inspection. The cartilage samples were stained using von Kossa/Safranin-orange staining. These stainings were used for OA severity scoring using the OARSI-Score. Chondrocyte differentiation markers were evaluated using Collagen 2 and X, as well as Sox9 and aggrecan as markers for chondrocyte hypertrophic differentiation in immunohistochemistry and qRT-PCR. ß-Galactosidase, p16 and p21 staining was used to investigate the activation of senescence on crystal stimulated chondrocytes. In vivo results were validated using qRT-PCR for the expression of the phenotypic marker genes after stimulation of C28 chondrocytes with CPPD and BCP crystals.
Results: Radiologically detectable cartilage calcifications were evident in CC patients, but absent in OA patients without CC. Histological OA severity was lower in patients with CC compared to OA patients without CC. Immunohistological stainings showed a hypertrophic differentiation of chondrocytes in OA cartilage without CC. This could not be observed in CC cartilage. qRT-PCR indicated no relevant influence of CPPD crystals on hypertrophic marker genes, whereas BCP crystals significantly induced hypertrophic differentiation. However, CPPD crystals seemed to induce chondrocyte senescence, which was not observed after stimulation with BCP crystals.
Conclusion: BCP and CPPD crystals seem to trigger differential effects on the chondrocyte phenotype. BCP crystals induce hypertrophic differentiation of chondrocytes, whereas CPPD crystals seem to induce senescence.