title: Nurse-like cells from patients with rheumatoid arthritis support the survival of osteoclast precursors via macrophage colony-stimulating factor production.
abstract: OBJECTIVE
  To elucidate the role of nurse-like cells (NLCs) obtained from rheumatoid arthritis (RA) patients in bone loss during progressive synovial expansion.
  
  
  METHODS
  CD14+ monocytes were cocultured with NLCs for 4 weeks and collected as NLC-supported CD14+ (NCD14+) monocytes. To determine their ability to differentiate into osteoclasts, NCD14+ monocytes were further cultured with macrophage colony-stimulating factor (M-CSF) together with RANKL or tumor necrosis factor alpha (TNFalpha). NCD14+ monocytes were also cocultured with SaOS-4/3 cells, which were shown to support osteoclastogenesis in response to parathyroid hormone (PTH). CD14+ monocytes were cocultured with SaOS-4/3 cells to elucidate how SaOS-4/3 cells and NLCs supported CD14+ monocytes for a long period. Synovial expansion adjacent to bone in RA patients was examined immunohistochemically to detect osteoclast precursors such as NCD14+ monocytes.
  
  
  RESULTS
  NLCs supported the survival of CD14+ monocytes for 4 weeks. NCD14+ as well as CD14+ monocytes differentiated into osteoclasts in the presence of M-CSF together with RANKL or TNFalpha. NCD14+ monocytes also differentiated into osteoclasts in PTH-treated cocultures with SaOS-4/3 cells. SaOS-4/3 cells supported the survival of CD14+ monocytes for 4 weeks in the presence, but not absence, of PTH. Treatment of SaOS-4/3 cells with PTH up-regulated the expression of M-CSF messenger RNA. Neutralizing antibodies against M-CSF inhibited the NLC-supported survival of CD14+ monocytes. CD68+ monocytes and M-CSF+ fibroblast-like synoviocytes were colocalized in regions adjacent to the destroyed bone of RA patients.
  
  
  CONCLUSIONS
  Our findings suggest that NLCs are involved in RA-induced bone destruction by maintaining osteoclast precursors via production of M-CSF.
authors.affiliation: Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Jun
authors.initials: J
authors.lastname: Hashimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochi
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D016173:Macrophage Colony-Stimulating Factor