title: Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis.
abstract: OBJECTIVE
  Osteoarthritis (OA) is accompanied by subchondral bone sclerosis. The present study was undertaken to determine whether osteoblast-like cells in patients with OA show an abnormal phenotype that could contribute to this sclerosis.
  
  
  METHODS
  Explants and primary in vitro osteoblast-like cell cultures were prepared from subchondral bone specimens from OA patients or from bone removed at autopsy from individuals showing no signs of OA or metabolic bone disease. We measured the abundance and activity of urokinase plasminogen activator (uPA), and the levels of PA inhibitor (PAI-1) and insulin-like growth factor 1 (IGF-1) in conditioned media from both explants and osteoblast-like cells. The expression of osteoblast phenotypic biomarkers was also evaluated.
  
  
  RESULTS
  OA explants showed increased levels and activity of uPA, no changes in PAI-1 abundance, and increases in IGF-1 release, as compared with preparations from normal individuals. In vitro primary osteoblast-like cells showed results similar to the ex vivo findings for uPA, PAI-1, and IGF-1. Primary OA osteoblast-like cells also expressed higher alkaline phosphatase activity and osteocalcin release than normal cells, both under basal conditions and with 1,25(OH)2D3 (1,25-dihydroxyvitamin D) stimulation. Conversely, OA osteoblast-like cells showed blunted cAMP synthesis in response to human parathyroid hormone and prostaglandin E2 in contrast to the finding with normal osteoblast-like cells, a result that could not be attributed to altered adenylate cyclase activity.
  
  
  CONCLUSIONS
  Ex vivo and in vitro results indicate similar altered activities of OA osteoblasts as compared with normal cells. This suggests that an altered phenotype of subchondral osteoblasts may be a contributing factor in human OA.
authors.affiliation: Centre de Recherche L. C. Simard, Centre Hospitalier de l'Université de Montréal, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Hilal
authors.forename: J
authors.initials: J
authors.lastname: Martel-Pelletier
authors.forename: J P
authors.initials: JP
authors.lastname: Pelletier
authors.forename: P
authors.initials: P
authors.lastname: Ranger
authors.forename: D
authors.initials: D
authors.lastname: Lajeunesse
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D009924:Organ Culture Techniques; D010003:Osteoarthritis / Q000150:complications / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D010026:Osteosclerosis / Q000209:etiology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D010281:Parathyroid Hormone; D017395:Plasminogen Activator Inhibitor 1; D015675:Osteocalcin; C025169:1,25-dihydroxy-previtamin D(3); D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D014568:Urokinase-Type Plasminogen Activator; D002117:Calcitriol; D015232:Dinoprostone