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

Osteoarthritis Cartilage. 2012 Nov;20(11):1399-408. doi: 10.1016/j.joca.2012.07.017. Epub 2012 Aug 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Phosphates / metabolism
  • Calcium Phosphates / pharmacology*
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Cattle
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology*
  • Crystallization
  • Drug Antagonism
  • Female
  • Proteoglycans / metabolism


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