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Hamamura K, Nishimura A, Iino T, et al. Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis. Bone Joint Res. 2015;4(5):84-92doi: 10.1302/2046-3758.45.2000378.
Hamamura, 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. https://doi.org/10.1302/2046-3758.45.2000378
Hamamura, K, et al. "Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis." Bone & joint research vol. 4,5 (2015): 84-92. doi: https://doi.org/10.1302/2046-3758.45.2000378
Hamamura K, Nishimura A, Iino T, Takigawa S, Sudo A, Yokota H. Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis. Bone Joint Res. 2015 May;4(5):84-92. doi: 10.1302/2046-3758.45.2000378. PMID: 25977571; PMCID: PMC4443296.
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Bone Joint Res. 2015 May;4(5):84-92. doi: 10.1302/2046-3758.45.2000378.

Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis.

Bone & joint research

K Hamamura, A Nishimura, T Iino, S Takigawa, A Sudo, H Yokota

Affiliations

  1. Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA.
  2. Indiana University, Purdue University, Indianapolis, 723 West Michigan Street, Indianapolis, Indiana 46202, USA. Mie University Graduate School of Medicine, Mie 514, Japan.
  3. Mie University Graduate School of Medicine, Mie 514, Japan.

PMID: 25977571 PMCID: PMC4443296 DOI: 10.1302/2046-3758.45.2000378

Abstract

OBJECTIVES: 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.

©2015 The British Editorial Society of Bone & Joint Surgery.

Keywords: Cartilage; MMP13; NFkappaB; Osteoarthritis; Salubrinal

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