PMID- 22885567
OWN - NLM
STAT- MEDLINE
DCOM- 20130307
LR  - 20161018
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 20
IP  - 11
DP  - 2012 Nov
TI  - Intracellular calcium oscillations in articular chondrocytes induced by basic 
      calcium phosphate crystals lead to cartilage degradation.
PG  - 1399-408
LID - S1063-4584(12)00906-5 [pii]
LID - 10.1016/j.joca.2012.07.017 [doi]
AB  - 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, iCa(2)(+) 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.
CI  - Copyright (c) 2012 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Nguyen, C
AU  - Nguyen C
AD  - Univ Paris Diderot, Sorbonne Paris Cite, INSERM, UMR-S 606, F-75205 Paris, 
      France.
FAU - Lieberherr, M
AU  - Lieberherr M
FAU - Bordat, C
AU  - Bordat C
FAU - Velard, F
AU  - Velard F
FAU - Come, D
AU  - Come D
FAU - Liote, F
AU  - Liote F
FAU - Ea, H-K
AU  - Ea HK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120808
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Phosphates)
RN  - 0 (Proteoglycans)
RN  - 97Z1WI3NDX (calcium phosphate)
SB  - IM
MH  - Animals
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Phosphates/metabolism/*pharmacology
MH  - Calcium Signaling/*drug effects/physiology
MH  - Cartilage, Articular/drug effects/metabolism/*pathology
MH  - Cattle
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/metabolism/*pathology
MH  - Crystallization
MH  - Drug Antagonism
MH  - Female
MH  - Proteoglycans/metabolism
EDAT- 2012/08/14 06:00
MHDA- 2013/03/08 06:00
CRDT- 2012/08/14 06:00
PHST- 2011/11/21 00:00 [received]
PHST- 2012/07/18 00:00 [revised]
PHST- 2012/07/25 00:00 [accepted]
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/03/08 06:00 [medline]
AID - S1063-4584(12)00906-5 [pii]
AID - 10.1016/j.joca.2012.07.017 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2012 Nov;20(11):1399-408. doi: 
      10.1016/j.joca.2012.07.017. Epub 2012 Aug 8.