Yang Chunxi, Madhu Vedavathi, Thomas Candace, Yang Xinlin, Du Xeujun, Dighe Abhijit S, Cui Quanjun
Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital (Tenth People's Hospital of Tongji University), Shanghai, 200072, China.
Cell Tissue Res. 2015 Dec;362(3):577-85. doi: 10.1007/s00441-015-2245-1. Epub 2015 Jul 30.
Dimethyl sulfoxide (DMSO) is an FDA-approved organosulfur solvent that is reported to have therapeutic value in osteoarthritis and osteopenia. DMSO is used as a cryoprotectant for the cryopreservation of bone grafts and mesenchymal stem cells which are later used for bone repair. It is also used as a solvent in the preparation of various scaffolds used for bone tissue engineering purposes. DMSO has been reported to inhibit osteoclast formation in vitro but the mechanism involved has remained elusive. We investigated the effect of DMSO on osteoclast differentiation and function using a conventional model system of RAW 264.7 cells. The differentiation of RAW 264.7 cells was induced by adding 50 ng/ml RANKL and the effect of DMSO (0.01 and 1% v/v) on RANKL-induced osteoclastogenesis was investigated. Addition of 1% DMSO significantly inhibited RANKL-induced formation of TRAP+, multinucleated, mature osteoclasts and osteoclast late-stage precursors (c-Kit(-) c-Fms(+) Mac-1(+) RANK(+)). While DMSO did not inhibit proliferation per se, it did inhibit the effect of RANKL on proliferation of RAW 264.7 cells. Key genes related to osteoclast function (TRAP, Integrin αVβ3, Cathepsin K and MMP9) were significantly down-regulated by DMSO. RANKL-induced expression of RANK gene was significantly reduced in the presence of DMSO. Our data, and reports from other investigators, that DMSO enhances osteoblastic differentiation of mesenchymal stem cells and also prevents bone loss in ovarietcomized rats, suggest that DMSO has tremendous potential in the treatment of osteoporosis and bone diseases arising from uncontrolled activities of the osteoclasts.
二甲基亚砜（DMSO）是一种经美国食品药品监督管理局（FDA）批准的有机硫溶剂，据报道在骨关节炎和骨质减少方面具有治疗价值。DMSO用作骨移植和间充质干细胞冷冻保存的冷冻保护剂，这些细胞随后用于骨修复。它还用作制备用于骨组织工程目的的各种支架的溶剂。据报道，DMSO在体外可抑制破骨细胞形成，但其涉及的机制仍不清楚。我们使用RAW 264.7细胞的传统模型系统研究了DMSO对破骨细胞分化和功能的影响。通过添加50 ng/ml的核因子κB受体活化因子配体（RANKL）诱导RAW 264.7细胞分化，并研究了DMSO（0.01%和1% v/v）对RANKL诱导的破骨细胞生成的影响。添加1%的DMSO可显著抑制RANKL诱导的抗酒石酸酸性磷酸酶（TRAP）阳性、多核成熟破骨细胞和破骨细胞晚期前体（c-Kit(-) c-Fms(+) Mac-1(+) RANK(+)）的形成。虽然DMSO本身不抑制增殖，但它确实抑制了RANKL对RAW 264.7细胞增殖的影响。与破骨细胞功能相关的关键基因（TRAP、整合素αVβ3、组织蛋白酶K和基质金属蛋白酶9）被DMSO显著下调。在DMSO存在下，RANKL诱导的RANK基因表达显著降低。我们的数据以及其他研究者的报告表明，DMSO可增强间充质干细胞的成骨细胞分化，并预防去卵巢大鼠的骨质流失，这表明DMSO在治疗骨质疏松症和由破骨细胞不受控制的活动引起的骨疾病方面具有巨大潜力。
