title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, INSERM, UMR-S 606, F-75205 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: Lieberherr
authors.forename: C
authors.initials: C
authors.lastname: Bordat
authors.forename: F
authors.initials: F
authors.lastname: Velard
authors.forename: D
authors.initials: D
authors.lastname: Côme
authors.forename: F
authors.initials: F
authors.lastname: Lioté
authors.forename: H-K
authors.initials: HK
authors.lastname: Ea
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002130:Calcium Phosphates / Q000378:metabolism / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D003460:Crystallization; D004336:Drug Antagonism; D005260:Female; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D002130:Calcium Phosphates; D011509:Proteoglycans; C020243:calcium phosphate