Skip to Main content Skip to Navigation
Journal articles

Pathogenic Role of Basic Calcium Phosphate Crystals in Destructive Arthropathies

Abstract : Background: basic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals. Methodology/ Principal Findings synovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1α -/- and IL-1β-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1α and IL-1β signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1α or IL-1β. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages. Conclusions/ Significance intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome.
Complete list of metadatas

Cited literature [35 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01472876
Contributor : Gestionnaire Hal-Upmc <>
Submitted on : Tuesday, February 21, 2017 - 2:12:51 PM
Last modification on : Friday, October 30, 2020 - 2:40:03 PM
Long-term archiving on: : Monday, May 22, 2017 - 3:27:03 PM

File

journal.pone.0057352.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Hang Korng Ea, Véronique Chobaz, Christelle Nguyen, Sonia Nasi, Peter van Lent, et al.. Pathogenic Role of Basic Calcium Phosphate Crystals in Destructive Arthropathies. PLoS ONE, Public Library of Science, 2013, 8 (2), pp.e57352. ⟨10.1371/journal.pone.0057352.s001⟩. ⟨hal-01472876⟩

Share

Metrics

Record views

819

Files downloads

710