Titre

Pathogenic role of basic calcium phosphate crystals in destructive arthropathies.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Ea, H.K.
Auteure/Auteur
Chobaz, V.
Auteure/Auteur
Nguyen, C.
Auteure/Auteur
Nasi, S.
Auteure/Auteur
van Lent, P.
Auteure/Auteur
Daudon, M.
Auteure/Auteur
Dessombz, A.
Auteure/Auteur
Bazin, D.
Auteure/Auteur
McCarthy, G.
Auteure/Auteur
Jolles-Haeberli, B.
Auteure/Auteur
Ives, A.
Auteure/Auteur
Van Linthoudt, D.
Auteure/Auteur
So, A.
Auteure/Auteur
Lioté, F.
Auteure/Auteur
Busso, N.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2013
Volume
8
Numéro
2
Première page
e57352
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
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.
PID Serval
serval:BIB_D926771C9DE9
DOI
PMID
WOS
Permalien
Open Access
Oui
Date de création
2013-04-12T16:49:59.450Z
Date de création dans IRIS
2025-05-20T21:54:31Z
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BIB_D926771C9DE9.P001.pdf

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preprint

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882.54 KB

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Adobe PDF

PID Serval

serval:BIB_D926771C9DE9.P001

URN

urn:nbn:ch:serval-BIB_D926771C9DE94

Somme de contrôle

(MD5):84fd555fe04fc501ee59cf4b0ce18d16