Osteoclast-like cell formation by circulating myeloma B lymphocytes: Role of RANK-L
Osteoclast-like cell formation by circulating myeloma B lymphocytes: Role of RANK-L
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DOI：
10.1080/10428190310001595696
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发表时间：
2004-02-01
影响因子：
2.6
通讯作者：
Dammacco, F
中科院分区：
文献类型：
--
作者：
Calvani, N;Silvestris, F;Dammacco, F
多发性骨髓瘤 (MM) 是一种 B 淋巴起源的恶性肿瘤，其过度骨吸收是通过破骨细胞介导的，破骨细胞对骨髓微环境中肿瘤细胞产生的局部破骨细胞激活因子做出反应。由于最近在小鼠中假设 B 淋巴细胞和破骨细胞分化途径之间存在联系，因此本研究研究了骨髓瘤细胞的直接骨吸收。从 10 名患有多处溶骨性病变的骨髓瘤患者和 10 名健康供体中分离出的外周 CD19 + B 淋巴细胞在 M-CSF 和 RANK-L（两种主要破骨细胞激活因子）存在的情况下进行培养。 TRAP表达和骨基质吸收用于评估破骨细胞分化。 MM 患者的特点是存在循环 B 淋巴细胞，当 RANK-L 刺激时，其在体外具有破骨细胞样细胞的表型和功能特性。健康捐献者的 B 淋巴细胞缺乏这些特征，表明这种转化可归因于 MM 患者中克隆性 B 细胞的存在。克隆型 B 淋巴细胞可能通过充当 RANK-L 依赖性破骨细胞祖细胞来促进 MM 骨病的发病机制。
Excessive bone resorption in multiple myeloma (MM), a malignancy of B lymphoid origin, is mediated through osteoclasts, which respond to local osteoclast-activating factors produced by tumor cells within the bone marrow microenvironment. Direct bone resorption by myeloma cells is investigated in the present study, since a connection between B lymphocytes and osteoclast differentiation pathways has been recently postulated in mice. Peripheral CD19 + B lymphocytes isolated from 10 myeloma patients with multiple osteolytic lesions and 10 healthy donors were cultured in the presence of M-CSF and RANK-L, two major osteoclast-activating factors. The TRAP expression and resorption of bone substrates were employed to evaluate osteoclast differentiation. MM patients were characterized by the presence of circulating B lymphocytes endowed with both phenotypical and functional properties of osteoclast-like cells in vitro when stimulated with RANK-L. The absence of these characteristics in B lymphocytes from healthy donors indicates that the transformation can be ascribed to the presence of clonogenic B cells in patients with MM. Clonotypic B lymphocytes may contribute to the pathogenesis of bone disease in MM by acting as RANK-L-dependent osteoclast progenitors.