Calcification of cartilage is a common finding during osteoarthritis (OA). We have shown that it is mainly of the BCP type and not the CPPD type of crystal formation. BCP cartilage calcification is directly linked to the severity of cartilage degradation and, therefore, OA severity. We have also shown that with increasing hypertrophic differentiation of chondrocytes, the amount of calcification increases in vivo and in vitro. This indicates a link between chondrocyte hypertrophy andcartilage calcification. The pyrophosphate pathway is known to be involved in tissue calcification. It functions to keep the sensitive balance of pyrophosphate (PPi) and phosphate (Pi), thereby preventing the generation of calcium-phosphate crystals. One key player in this pathway is the nucleotide pyrophosphatase phosphodiesterase (NPP1), which has been demonstrated to be regulated by inflammatory mediators such as IL-1. In our cohort of OA patients, the expression of collagen X and NPP1, but not ANK and TNAP, correlated with cartilage calcification and also with the Mankin-Score. NPP1 expression inverse correlated with the calcification, whereas collagen X was upregulated. This finding was confirmed in experimental murine OA using the DMM mouse model. Furthermore, NPP1mut/mut mice (ttw/ttw) exhibit more calcification activity than wild type controls in joints as well as in cartilage of non weight bearing areas, including ear cartilage, suggesting that mechanical stress is not required for the induction of calcification. NPP1mut/mut (ttw/ttw) mice developed typical OA-like changes as evaluated by histological analysis as well as in vivo imaging and histological stainings. Intriguingly, calcification was associated with increased expression of the hypertrophic cartilage marker collagen X and the bone marker collagen I. Additionally, BCP crystals are able to activate chondrocyte differentiation via the WNT signaling pathway.
NPP1 is an important player in OA-associated cartilage calcification. Pathologic calcification of cartilage resembles in many aspects cartilage transformation into bone. Taken together, the data suggest that OA is characterized by the re-activation of molecular signalling cascades that at least in part resemble endochondral ossification.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.