Sodium Thiosulfate Prevents Chondrocyte Mineralization and Reduces the Severity of Murine Osteoarthritis.

Sonia Nasi,Hang-Korng Ea,Alexander So,Frédéric Lioté,Nathalie Busso

doi:10.1371/journal.pone.0158196

Sonia Nasi, Hang-Korng Ea + Show 3 more

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https://doi.org/10.1371/journal.pone.0158196

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Abstract

ObjectivesCalcium-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.MethodsHydroxyapatite (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.ResultsIn 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.ConclusionsSTS 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.

Highlights

Osteoarthritis (OA) is a joint disease, characterized by degeneration of articular cartilage, osteophytes formation and synovial lining hyperplasia [1, 2]
sodium thiosulfate (STS) prevented in a dose-dependent manner calcium crystal deposition in chondrocytes and inhibited Annexin V gene expression
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 crystalinduced inflammation as well as catabolic enzymes and reactive oxygen species (ROS) generation

Summary

Introduction

Osteoarthritis (OA) is a joint disease, characterized by degeneration of articular cartilage, osteophytes formation and synovial lining hyperplasia [1, 2]. OA affects millions of people worldwide and is the most prevalent cause of disability in the elderly As such, it represents a major medical, economic and social challenge for aging societies. The importance of BCP crystals in OA pathogenesis was recently demonstrated through intra-articular injection of BCP crystals which led to a chronic arthropathy in mice characterized by low grade inflammation and cartilage degradation [13]. In menisectomized mice, a validated model of OA, we observed an accumulation of joint calcific deposits in the form of BCP crystals. In this model, crystal deposition correlated with cartilage degradation and IL-6 expression [14]. Compounds that interfere with crystal deposition ought to bring therapeutic benefit in the context of OA

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