title: Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors.
abstract: BACKGROUND
  Ankylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, andin vitroosteoclast differentiation in AS patients.
  
  
  METHODS
  Patients with active AS without any ongoing therapy and age- and gender-matched healthy donors were recruited. Receptor activator of nuclear factor-κβ (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations were assessed. Quantification of serum levels of bone turnover markers and cytokines,in vitroOC differentiation assay and quantitative reverse transcription real-time PCR for OC-specific genes were performed.
  
  
  RESULTS
  Pro- and anti-inflammatory cytokine serum levels were higher in AS patients than in controls. RANKL neutrophil expression was higher in AS patients when compared to healthy donors, but CD51/CD61 expression was lower in the classical monocyte subpopulation. Concerning osteoclastogenesis, we found no differences in thein vitroosteoclast differentiating potential of these cells when compared to healthy donors. However, we observed low expression of CSF1R, RANK, and NFATc1 in AS OCPs.
  
  
  CONCLUSIONS
  Despite the high levels of pro-inflammatory cytokines present in AS patients, no differences in the number of OC or resorbed area were found between AS patients and healthy donors. Moreover, we observed that OCPs have low OC-specific gene expression. These findings support our hypothesis of an impaired response of OCPs to pro-osteoclastogenic stimuliin vivoin AS patients.
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa , Lisboa , Portugal.
authors.forename: Inês P
authors.initials: IP
authors.lastname: Perpétuo
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa , Lisboa , Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon Academic Medical Centre, Lisboa, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Vieira-Sousa
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon Academic Medical Centre, Lisboa, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Campanilho-Marques
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon Academic Medical Centre, Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ponte
authors.affiliation: EpiDoC Unit, Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade Nova de Lisboa , Lisboa , Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.affiliation: Musculoskeletal Diseases and Inflammation Research Group, Biomedicum Helsinki 1, Faculty of Medicine, Institute of Clinical Medicine, University of Helsinki , Helsinki , Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Ainola
authors.affiliation: Rheumatology Research Unit, Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal; Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon Academic Medical Centre, Lisboa, Portugal.
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
keywords: CSF1R; NFATc1; RANK; ankylosing spondylitis; gene expression; humans; monocytes; osteoclasts