title: Sodium Thiosulfate Prevents Chondrocyte Mineralization and Reduces the Severity of Murine Osteoarthritis.
abstract: OBJECTIVE
  Calcium-containing crystals participate in the pathogenesis of OA. Sodium thiosulfate (STS) has been shown to be an effective treatment in calcification disorders such as calciphylaxis and vascular calcification. This study investigated the effects and mechanisms of action of STS in a murine model of OA and in chondrocyte calcification.
  
  
  METHODS
  Hydroxyapatite (HA) crystals-stimulated murine chondrocytes and macrophages were treated with STS. Mineralization and cellular production of IL-6, MCP-1 and reactive oxygen species (ROS) were assayed. STS's effects on genes involved in calcification, inflammation and cartilage matrix degradation were studied by RT-PCR. STS was administered in the menisectomy model of murine OA, and the effect on periarticular calcific deposits and cartilage degeneration was investigated by micro-CT-scan and histology.
  
  
  RESULTS
  In vitro, STS prevented in a dose-dependent manner calcium crystal deposition in chondrocytes and inhibited Annexin V gene expression. In addition, there was a reduction in crystal-induced IL-6 and MCP-1 production. STS also had an antioxidant effect, diminished HA-induced ROS generation and abrogated HA-induced catabolic responses in chondrocytes. In vivo, administration of STS reduced the histological severity of OA, by limiting the size of new periarticular calcific deposits and reducing the severity of cartilage damage.
  
  
  CONCLUSIONS
  STS reduces the severity of periarticular calcification and cartilage damage in an animal model of OA via its effects on chondrocyte mineralization and its attenuation of crystal-induced inflammation as well as catabolic enzymes and ROS generation. Our study suggests that STS may be a disease-modifying drug in crystal-associated OA.
authors.affiliation: Service of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Nasi
authors.affiliation: Hospital Lariboisière, Service of Rheumatology, University School of Medicine, Paris VII, Paris, France.
authors.forename: Hang-Korng
authors.initials: HK
authors.lastname: Ea
authors.affiliation: Hospital Lariboisière, Service of Rheumatology, University School of Medicine, Paris VII, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lioté
authors.affiliation: Service of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: So
authors.affiliation: Service of Rheumatology, Department of Musculoskeletal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000737:chemistry; D002130:Calcium Phosphates / Q000737:chemistry; D002356:Cartilage / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology*; D003460:Crystallization; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: C111835:CCL2 protein, human; D002130:Calcium Phosphates; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C508600:IL6 protein, human; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013885:Thiosulfates; C577686:interleukin-6, mouse; C020243:calcium phosphate; C017717:sodium thiosulfate; D002118:Calcium