Tsuboi Hideki, Udagawa Nobuyuki, Hashimoto Jun, Yoshikawa Hideki, Takahashi Naoyuki, Ochi Takahiro
Osaka University Graduate School of Medicine, Suita, Japan.
Arthritis Rheum. 2005 Dec;52(12):3819-28. doi: 10.1002/art.21425.
To elucidate the role of nurse-like cells (NLCs) obtained from rheumatoid arthritis (RA) patients in bone loss during progressive synovial expansion.
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.
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.
Our findings suggest that NLCs are involved in RA-induced bone destruction by maintaining osteoclast precursors via production of M-CSF.
阐明从类风湿关节炎（RA）患者中获得的类成骨细胞（NLCs）在进行性滑膜扩张过程中骨质流失中的作用。
将CD14+单核细胞与NLCs共培养4周，并收集作为NLC支持的CD14+（NCD14+）单核细胞。为了确定它们分化为破骨细胞的能力，将NCD14+单核细胞与巨噬细胞集落刺激因子（M-CSF）以及RANKL或肿瘤坏死因子α（TNFα）进一步培养。NCD14+单核细胞也与SaOS-4/3细胞共培养，已证明SaOS-4/3细胞可响应甲状旁腺激素（PTH）支持破骨细胞生成。将CD14+单核细胞与SaOS-4/3细胞共培养，以阐明SaOS-4/3细胞和NLCs如何长期支持CD14+单核细胞。对RA患者骨旁的滑膜扩张进行免疫组织化学检查，以检测破骨细胞前体，如NCD14+单核细胞。
NLCs支持CD14+单核细胞存活4周。在存在M-CSF以及RANKL或TNFα的情况下，NCD14+以及CD14+单核细胞分化为破骨细胞。在与SaOS-4/3细胞的PTH处理共培养中，NCD14+单核细胞也分化为破骨细胞。在存在但不存在PTH的情况下，SaOS-4/3细胞支持CD14+单核细胞存活4周。用PTH处理SaOS-4/3细胞可上调M-CSF信使核糖核酸的表达。针对M-CSF的中和抗体抑制了NLC支持的CD14+单核细胞的存活。CD68+单核细胞和M-CSF+成纤维样滑膜细胞在RA患者受损骨附近区域共定位。
我们的研究结果表明，NLCs通过产生M-CSF维持破骨细胞前体，从而参与RA诱导的骨破坏。
