Document Detail


Intracellular calcium oscillations in articular chondrocytes induced by basic calcium phosphate crystals lead to cartilage degradation.
MedLine Citation:
PMID:  22885567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Basic calcium phosphate (BCP) crystals, including octacalcium phosphate (OCP), carbonated-apatite (CA) and hydroxyapatite (HA) crystals are associated with destructive forms of osteoarthritis. Mechanisms of BCP-induced cartilage breakdown remain incompletely understood. We assessed the ability of BCP to induce changes in intracellular calcium (iCa(2+)) content and oscillations and the role of iCa(2+) in BCP-induced cartilage degradation.
METHODS: Bovine articular chondrocytes (BACs) and bovine cartilage explants (BCEs) were stimulated with BCP or monosodium urate (MSU) crystals. iCa(2+) levels were determined by spectrofluorimetry and oscillations by confocal microscopy. mRNA expression of matrix metalloproteinase 3 (MMP-3), a disintegrin and metalloprotease with thrombospondin-like motifs 4 (ADAMTS-4) and ADAMTS-5 was assessed by quantitative real-time PCR. Glycosaminoglycan (GAG) release was measured in the supernatants of BCE cultures.
RESULTS: All three BCP crystals significantly increased iCa(2+) content. OCP also induced iCa(2+) oscillations. Rate of BACs displaying iCa(2+) oscillations increased over time, with a peak after 20 min of stimulation. OCP-induced iCa(2+) oscillations involved both extracellular Ca(2+) (eCa(2+)) influx and iCa(2+) stores. Indeed, OCP-induced iCa(2+) oscillations decreased rapidly in Ca(2+)-free medium. Both voltage- and non-voltage-dependent Ca(2+) channels were involved in eCa(2+) influx. BCP crystal-induced variation in iCa(2+) content was associated with BCP crystal-induced cartilage matrix degradation. However, iCa²(+) was not associated with OCP crystal-induced mRNA expression of MMP-3, ADAMTS-4 or ADAMTS-5.
CONCLUSION: BCP crystals can induce variation in iCa(2+) content and oscillations in articular chondrocytes. Furthermore, BCP crystal-induced changes in iCa(2+) content play a pivotal role in BCP catabolic effects on articular cartilage.
Authors:
C Nguyen; M Lieberherr; C Bordat; F Velard; D Côme; F Lioté; H-K Ea
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-08
Journal Detail:
Title:  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society     Volume:  20     ISSN:  1522-9653     ISO Abbreviation:  Osteoarthr. Cartil.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-09-21     Completed Date:  2013-03-07     Revised Date:  2013-04-05    
Medline Journal Info:
Nlm Unique ID:  9305697     Medline TA:  Osteoarthritis Cartilage     Country:  England    
Other Details:
Languages:  eng     Pagination:  1399-408     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Univ Paris Diderot, Sorbonne Paris Cité, INSERM, UMR-S 606, F-75205 Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Channel Blockers / pharmacology
Calcium Phosphates / metabolism,  pharmacology*
Calcium Signaling / drug effects*,  physiology
Cartilage, Articular / drug effects,  metabolism,  pathology*
Cattle
Cells, Cultured
Chondrocytes / drug effects,  metabolism,  pathology*
Crystallization
Drug Antagonism
Female
Proteoglycans / metabolism
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Calcium Phosphates; 0/Proteoglycans; 97Z1WI3NDX/calcium phosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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