Hamamura, K.Nishimura, A.Iino, T.Takigawa, S.Sudo, A.Yokota, H.2016-06-152016-06-152015-05Hamamura, K., Nishimura, A., Iino, T., Takigawa, S., Sudo, A., & Yokota, H. (2015). Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis. Bone & Joint Research, 4(5), 84–92. http://doi.org/10.1302/2046-3758.45.2000378https://hdl.handle.net/1805/9971OBJECTIVES: Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). METHODS: OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. RESULTS: Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. CONCLUSIONS: Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84-92.en-USPublisher PolicySalubrinalOsteoarthritisMMP13NFkappaBCartilageArticle