title: Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hamamura
authors.affiliation: Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA. Mie University Graduate School of Medicine, Mie 514, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Mie University Graduate School of Medicine, Mie 514, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iino
authors.affiliation: Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Takigawa
authors.affiliation: Mie University Graduate School of Medicine, Mie 514, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sudo
authors.affiliation: Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yokota
keywords: Cartilage; MMP13; NFkappaB; Osteoarthritis; Salubrinal