Tumor necrosis factor-alpha alters the modulatory effects of mesenchymal stem cells on osteoclast formation and function.
Tumor necrosis factor-alpha alters the modulatory effects of mesenchymal stem cells on osteoclast formation and function.
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DOI：
10.1089/scd.2009.0021
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发表时间：
2009-12
影响因子：
4
通讯作者：
Heng Zhu;Xiao-Xia Jiang;Zi-Kuan Guo;Hong Li;Yong-feng Su;Hui-yu Yao;Xiao-Yan Wang;Xiusen Li;Ying Wu;Yuanlin Liu;Yi Zhang;N. Mao
中科院分区：
文献类型：
--
作者：
Heng Zhu;Xiao-Xia Jiang;Zi-Kuan Guo;Hong Li;Yong-feng Su;Hui-yu Yao;Xiao-Yan Wang;Xiusen Li;Ying Wu;Yuanlin Liu;Yi Zhang;N. Mao
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有造血支持和免疫抑制功能，而破骨细胞是骨内膜造血干细胞龛的主要细胞成分，在骨免疫学中起着关键作用。为了阐明这2种细胞的相关性，在存在或不存在巨噬细胞集落刺激因子（M-CSF）和NF-κ B配体受体激活剂（RANKL）的情况下，将小鼠CD 11b（+）单核细胞培养在MSC层上。结果表明，MSC独立地支持破骨细胞的发育，并且这种作用被M-CSF和RANKL增强。有趣的是，肿瘤坏死因子-α（TNF-α）刺激的MSC转而抑制破骨细胞的形成，并保护象牙切片免受骨吸收。实时PCR和ELISA分析表明，在TNF-α刺激的MSC中，骨保护素在mRNA和蛋白水平的表达上调，至少部分通过激活促分裂原活化蛋白激酶途径。此外，TNF-α刺激的MSC保持其免疫表型，多潜能分化和免疫抑制特性。此外，用类风湿性关节炎患者的滑液处理的MSC调节与TNF-α水平密切相关的破骨细胞生成。本研究提示MSCs对破骨细胞具有双重调节作用，这一结果可能有助于了解MSCs在炎症性疾病中的作用。
Mesenchymal stem cells (MSCs) are characterized by their hematopoiesis-supporting and immunosuppressive capacity, while osteoclasts are main cell components in the endosteal hematopoietic stem cell niche and pivotal players in osteoimmunology. To clarify the association of these 2 kinds of cells, mouse CD11b(+) monocytes were cultured onto MSC layers in the presence or absence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). The results showed that MSCs independently supported osteoclast development and this effect was enhanced by M-CSF and RANKL. Interestingly, tumor necrosis factor-alpha (TNF-alpha)-stimulated MSCs turned to inhibit osteoclast formation and protect tusk slices from osteoclastic resorption. Real-time PCR and ELISA assays demonstrated that osteoprotegerin expression at both mRNA and protein levels in TNF-alpha-stimulated MSCs was up-regulated, at least partially by activating the mitogen-activated protein kinase pathway. Furthermore, TNF-alpha-stimulated MSCs maintained their immunophenotypic, multipotential differentiation and immunosuppressive characteristics. Moreover, MSCs treated with synovial fluid from rheumatoid arthritis patients modulated osteoclast generation in close relation with the TNF-alpha levels. This study suggests that MSCs exhibit dual modulatory function on osteoclasts and the result might shed light on understanding the involvement of MSCs in the inflammatory diseases.