title: Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO).
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.
authors.affiliation: 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.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
authors.forename: Vedavathi
authors.initials: V
authors.lastname: Madhu
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
authors.forename: Candace
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.|Department of Orthopaedic Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
authors.forename: Xeujun
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
authors.forename: Abhijit S
authors.initials: AS
authors.lastname: Dighe
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA. QC4Q@hscmail.mcc.virginia.edu.
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D016023:Integrins; D007527:Isoenzymes; D053245:RANK Ligand; D048029:TNF Receptor-Associated Factor 6; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9; D004121:Dimethyl Sulfoxide
keywords: DMSO; Osteoclasts; Osteoporosis; RANKL; RAW 264.7 cells