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Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO)

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Abstract

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.

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Acknowledgments

This work was supported by grants from the Orthopaedic Research and Education Foundation (OREF), the Musculoskeletal Transplant Foundation (MTF) and the Orthopaedic Trauma Association (OTA) to QC. CY was supported by a grant from the National Natural Science Foundation of China (81101344/HO604) during the course of this study.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA

    Chunxi Yang, Vedavathi Madhu, Candace Thomas, Xinlin Yang, Xeujun Du, Abhijit S Dighe & Quanjun Cui

  2. Department of Orthopaedic Surgery, Shanghai Tenth People’s Hospital (Tenth People’s Hospital of Tongji University), Shanghai, 200072, China

    Chunxi Yang

  3. Department of Orthopaedic Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China

    Xeujun Du

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  1. Chunxi Yang
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  2. Vedavathi Madhu
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  3. Candace Thomas
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  4. Xinlin Yang
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  5. Xeujun Du
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  6. Abhijit S Dighe
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  7. Quanjun Cui
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Correspondence to Quanjun Cui.

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Yang, C., Madhu, V., Thomas, C. et al. Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO). Cell Tissue Res 362, 577–585 (2015). https://doi.org/10.1007/s00441-015-2245-1

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  • DOI: https://doi.org/10.1007/s00441-015-2245-1

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