Nurse-like cells from patients with rheumatoid arthritis support the survival of osteoclast precursors via macrophage colony-stimulating factor production.
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.
Tsuboi
Hideki
H
Osaka University Graduate School of Medicine, Suita, Japan.
Udagawa
Nobuyuki
N
Hashimoto
Jun
J
Yoshikawa
Hideki
H
Takahashi
Naoyuki
N
Ochi
Takahiro
T
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
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D016173:Macrophage Colony-Stimulating Factor