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Cartilage calcification in osteoarthritis: mechanisms and clinical relevance

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From Nature Reviews Rheumatology

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Abstract

Pathological calcification of cartilage is a hallmark of osteoarthritis (OA). Calcification can be observed both at the cartilage surface and in its deeper layers. The formation of calcium-containing crystals, typically basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals, is an active, highly regulated and complex biological process that is initiated by chondrocytes and modified by genetic factors, dysregulated mitophagy or apoptosis, inflammation and the activation of specific cellular-signalling pathways. The links between OA and BCP deposition are stronger than those observed between OA and CPP deposition. Here, we review the molecular processes involved in cartilage calcification in OA and summarize the effects of calcium crystals on chondrocytes, synovial fibroblasts, macrophages and bone cells. Finally, we highlight therapeutic pathways leading to decreased joint calcification and potential new drugs that could treat not only OA but also other diseases associated with pathological calcification.

Key points

  • Cartilage calcification, consisting of basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals, is a hallmark of osteoarthritis (OA).

  • The extent of BCP calcification correlates with the histological severity of OA.

  • Calcium crystals are formed by chondrocytes undergoing hypertrophy, mitophagy or apoptosis in response to inflammation and ageing.

  • Crystals trigger responses in chondrocytes, fibroblasts and macrophages, leading to inflammation, cell death and cartilage catabolism.

  • Treatments that inhibit pathological calcification could be potential novel therapies for OA.

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Fig. 1: Mechanisms of crystal nucleation.
Fig. 2: Modulators of crystal nucleation and growth.
Fig. 3: Molecular pathways activated by BCP and CPP crystals in chondrocytes.
Fig. 4: Molecular pathways activated by BCP and CPP crystals on synovial fibroblasts.
Fig. 5: Contribution of calcium-containing crystals in OA pathogenesis and potential therapies.

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  1. Service of Rheumatology, Department of Musculoskeletal Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

    Ilaria Bernabei, Alexander So, Nathalie Busso & Sonia Nasi

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Bernabei, I., So, A., Busso, N. et al. Cartilage calcification in osteoarthritis: mechanisms and clinical relevance. Nat Rev Rheumatol 19, 10–27 (2023). https://doi.org/10.1038/s41584-022-00875-4

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