Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis
Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis
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DOI：
10.1038/labinvest.2013.152
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发表时间：
2014-03-01
影响因子：
5
通讯作者：
Kukita, Toshio
中科院分区：
文献类型：
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作者：
Takano, Toshio;Li, Yin-Ji;Kukita, Toshio
骨髓间充质干细胞（mesenchymal stem cells，MSCs）具有分化为多种细胞系的潜能。近年来研究表明，MSCs还具有抗炎和免疫调节功能。在这份报告中，我们研究了骨髓间充质干细胞在炎症性骨破坏的发展中的调节功能，在大鼠炎症性关节炎（AA大鼠）。从大鼠骨髓组织中分离MSC，在碱性FGF存在下扩增，并腹腔注射到AA大鼠中。MSC给药显著抑制炎症参数：肿胀评分、肿胀宽度和后爪厚度。放射学评价表明，MSC显着抑制骨破坏。组织学分析表明，骨髓间充质干细胞的管理显着抑制破骨细胞在AA大鼠。为了进一步描述其对破骨细胞生成的影响，将MSC加入到经历破骨细胞生成的体外骨髓培养物中。MSC显着抑制破骨细胞在这个系统中。通过RT-PCR评估MSC中趋化因子受体的表达，并使用transwell培养系统进行趋化性测定。MSC对MIP-1 α（CCL3）和SDF-1 α（CXCL12）表现出显著的趋化性，趋化因子优先在炎性骨破坏区域表达。此外，MSC表达IL-10和骨保护素，抑制破骨细胞生成的细胞因子。这些数据表明，在AA大鼠骨破坏区域招募MSC可以抑制炎性骨破坏，并提高MSC可能具有治疗关节炎中炎性骨破坏的潜力的可能性。
Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1 alpha (CCL3) and SDF-1 alpha (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis.