title: Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.
abstract: BACKGROUND
  Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage.
  
  
  METHODS
  We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients.
  
  
  RESULTS
  Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages.
  
  
  CONCLUSIONS
  CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.
authors.forename: Christelle
authors.initials: C
authors.lastname: Nguyen
authors.forename: Dominique
authors.initials: D
authors.lastname: Bazin
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
authors.forename: Aurore
authors.initials: A
authors.lastname: Chatron-Colliet
authors.forename: Didier
authors.initials: D
authors.lastname: Hannouche
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bianchi
authors.forename: Dominique
authors.initials: D
authors.lastname: Côme
authors.forename: Alexander
authors.initials: A
authors.lastname: So
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lioté
authors.forename: Hang-Korng
authors.initials: HK
authors.lastname: Ea
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D019645:Arthroplasty, Replacement, Knee; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D002131:Calcium Pyrophosphate / Q000737:chemistry / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000601:surgery / Q000648:ultrastructure; D002478:Cells, Cultured; D002805:Chondrocalcinosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D003460:Crystallization; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D008297:Male; D008855:Microscopy, Electron, Scanning; D020370:Osteoarthritis, Knee / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D028061:Phosphate Transport Proteins / Q000235:genetics / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: C498770:ANKH protein, human; D002130:Calcium Phosphates; D028061:Phosphate Transport Proteins; C020243:calcium phosphate; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D002118:Calcium; D002131:Calcium Pyrophosphate