title: Identification of two populations of osteoarthritic osteoblasts according to the 1,25[OH]₂ vitamin D₃ potency to stimulate osteocalcin.
abstract: BACKGROUND
  Few studies have tried to discriminate a differential behavior between osteoarthritic (OA) osteoblasts (Obs). Based on osteocalcin level, we aimed, in the present study, to evaluate the capacity of OA Obs for producing molecules of the Wnt/β-catenin signaling pathway.
  
  
  METHODS
  Human primary OA Obs (n=11) were exposed or not to 50 nM of 1,25 dihydroxyvitamin D3 (VitD3) for 24 h. Osteocalcin (OCN), TGF-β1, Dickkopf-related protein 2 (DKK2), R-spondin 2 (Rspo2), Wnt5b, and low density lipoprotein related-receptor 1 (LRP1) were evaluated by real time RT-PCR.
  
  
  RESULTS
  All samples responded to VitD3 as validated by the increase in OCN expression. However two populations of Obs were discriminated; one called "high responders" whose OCN stimulation was higher than 100 fold (mean 881 fold, p<0.01, n=5) and the second one whose stimulation was inferior to 100 fold (mean 47 fold, p<0.01, n=6), namely "low responders". In fact, high responders have a weaker basal expression of OCN. With regards to these two cell populations and in absence of VitD3 challenge, the expression level of TGF-β1 (15 fold, p<0.001), DKK2 (2.5 fold, p<0.002) and Wnt5b (5.5 fold, p<0.003) was higher in "high responders", meanwhile Rspo2 and LRP1 expression was unchanged. VitD3 exacerbated this pattern but corrected OCN expression and favored Wnt agonist expression.
  
  
  CONCLUSIONS
  We identified 2 populations of OA Obs according to the OCN expression under the control of VitD3. In addition under basal conditions, these 2 populations expressed differently TGF-β1, Wnt5b, DKK2, suggesting a heterogeneous differentiation and phenotype in Obs among OA patients.
authors.affiliation: UMR 7365, CNRS-Université de Lorraine, IMoPA, Vandœuvre-lés-Nancy, France.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: UMR 7365, CNRS-Université de Lorraine, IMoPA, Vandœuvre-lés-Nancy, France.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Unité de Recherche en Arthrose, Centre de Recherche de l'Université de Montréal (CR-CHUM), Montréal, QC, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lajeunesse
authors.affiliation: UMR 7365, CNRS-Université de Lorraine, IMoPA, Vandœuvre-lés-Nancy, France Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Mainard
authors.affiliation: UMR 7365, CNRS-Université de Lorraine, IMoPA, Vandœuvre-lés-Nancy, France Centre Hospitalier Universitaire, Nancy, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Jouzeau
authors.affiliation: UMR 7365, CNRS-Université de Lorraine, IMoPA, Vandœuvre-lés-Nancy, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Reboul
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D010006:Osteoblasts / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D015675:Osteocalcin; D002117:Calcitriol
keywords: Osteoarthritis; Wnt system; osteoblast; osteocalcin; vitamin D_3