title: Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: the In Vitro Osteoclast Differentiation in Arthritis study.
abstract: OBJECTIVE
  To compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals.
  
  
  METHODS
  PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14+ expression and induced to differentiate into osteoclasts over 3 weeks in vitro. We assessed the number of osteoclasts, their resorptive activity, osteoclast apoptosis, and expression of the following cytokine receptors: RANK, interleukin-1 receptor type I (IL-1RI), and IL-1RII. A ridge logistic regression classifier was developed to discriminate OA patients from controls.
  
  
  RESULTS
  PBMCs from OA patients gave rise to more osteoclasts that resorbed more bone surface than did PBMCs from controls. The number of CD14+ precursors was comparable in both groups, but there was less apoptosis in osteoclasts obtained from OA patients. Although no correlation was found between osteoclastogenic capacity and clinical or radiographic scores, levels of IL-1RI were significantly lower in cultures from patients with OA than in cultures from controls. Osteoclast apoptosis and expression levels of IL-1RI and IL-1RII were used to build a multivariate predictive model for OA.
  
  
  CONCLUSIONS
  During 3 weeks of culture under identical conditions, monocytes from patients with OA display enhanced capacity to generate osteoclasts compared to cells from controls. Enhanced osteoclastogenesis is accompanied by increased resorptive activity, reduced osteoclast apoptosis, and diminished IL-1RI expression. These findings support the possibility that generalized changes in bone metabolism affecting osteoclasts participate in the pathophysiology of OA.
authors.affiliation: Université de Sherbrooke and Centre de Recherche Clinique Étienne-Le Bel, Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Marianne
authors.initials: M
authors.lastname: Durand
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Komarova
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhargava
authors.forename: Diana P
authors.initials: DP
authors.lastname: Trebec-Reynolds
authors.forename: Keying
authors.initials: K
authors.lastname: Li
authors.forename: Cara
authors.initials: C
authors.lastname: Fiorino
authors.forename: Osama
authors.initials: O
authors.lastname: Maria
authors.forename: Noushin
authors.initials: N
authors.lastname: Nabavi
authors.forename: Morris F
authors.initials: MF
authors.lastname: Manolson
authors.forename: Rene E
authors.initials: RE
authors.lastname: Harrison
authors.forename: S Jeffrey
authors.initials: SJ
authors.lastname: Dixon
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Sims
authors.forename: Marcin J
authors.initials: MJ
authors.lastname: Mizianty
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kurgan
authors.forename: Sonia
authors.initials: S
authors.lastname: Haroun
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.forename: Maria
authors.initials: M
authors.lastname: de Fatima Lucena-Fernandes
authors.forename: Artur J
authors.initials: AJ
authors.lastname: de Brum-Fernandes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology*; D001862:Bone Resorption / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D018950:Lipopolysaccharide Receptors; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors