Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
J Pathol. 2011 Sep;225(1):151-6. doi: 10.1002/path.2937. Epub 2011 Jun 27.
Pigmented villonodular synovitis (PVNS) is a synovial tumour-like lesion that frequently causes osteolysis. PVNS contains numerous macrophages and osteoclast-like giant cells. In this study, we have analysed the cytochemical and functional characteristics of mononuclear and multinucleated cells in PVNS and determined the cellular and humoral mechanisms underlying giant cell formation and resorption in PVNS. Giant cells and CD14(+) and CD14(-) mononuclear cell populations were isolated from PVNS synovial tissue and cultured alone or in the presence and absence of the osteoclastogenic factors, RANKL and M-CSF. Osteoclast formation and activity was assessed by expression of TRAP and evidence of lacunar resorption. Giant cells in PVNS expressed an osteoclast-phenotype (CD51(+) , TRAP(+) , CD14(-) , HLA-DR(-) ) and were formed only in cultures of mononuclear cells that expressed the macrophage marker CD14. Osteoclast formation required RANKL and occurred in both the presence and absence of exogenous M-CSF. CD14(-) cells in PVNS expressed RANKL. Lacunar resorption by PVNS-derived giant cells was abolished by the addition of the bisphosphonate, zoledronate. Our findings indicate that osteoclasts form by a RANKL-dependent mechanism from CD14(+) mononuclear phagocytes in PVNS. Osteoclast formation occurred even in the absence of exogenous M-CSF, a finding which is in keeping with over-expression of M-CSF playing a pathogenic role in this condition. Anti-osteoclast resorptive treatment may be useful to control osteolysis in PVNS.
色素沉着绒毛结节性滑膜炎 (PVNS) 是一种滑膜肿瘤样病变，常导致溶骨性破坏。PVNS 含有大量巨噬细胞和破骨细胞样巨细胞。在本研究中，我们分析了 PVNS 中单核细胞和多核细胞的细胞化学和功能特征，并确定了巨细胞形成和吸收的细胞和体液机制。从 PVNS 滑膜组织中分离出巨细胞和 CD14(+)和 CD14(-)单核细胞群体，单独或在破骨细胞生成因子 RANKL 和 M-CSF 的存在和不存在下培养。通过表达 TRAP 和空泡吸收的证据来评估破骨细胞的形成和活性。PVNS 中的巨细胞表达破骨细胞表型 (CD51(+)、TRAP(+)、CD14(-)、HLA-DR(-))，仅在表达巨噬细胞标志物 CD14 的单核细胞培养物中形成。破骨细胞的形成需要 RANKL，并且在存在和不存在外源性 M-CSF 的情况下都会发生。PVNS 中的 CD14(-)细胞表达 RANKL。PVNS 来源的巨细胞的空泡吸收被双膦酸盐唑来膦酸的添加所抑制。我们的发现表明，PVNS 中的 RANKL 依赖性机制可从 CD14(+)单核吞噬细胞形成破骨细胞。即使在不存在外源性 M-CSF 的情况下也会发生破骨细胞形成，这一发现与 M-CSF 的过度表达在这种情况下发挥致病作用相一致。抗破骨细胞吸收治疗可能有助于控制 PVNS 中的溶骨性破坏。
