Intracellular calcium oscillations in articular chondrocytes induced by basic calcium phosphate crystals lead to cartilage degradation.

Abstract

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
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 20 Issue 11 Pg. 1399-408 (Nov 2012) ISSN: 1522-9653 [Electronic] England
• PMID: 22885567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Calcium Channel Blockers
• Calcium Phosphates
• Proteoglycans
• calcium phosphate

Topics

• 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)