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). 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.Objectives
Methods
Treatment for osteoarthritis (OA) has traditionally
focused on joint replacement for end-stage disease. An increasing number
of surgical and pharmaceutical strategies for disease prevention
have now been proposed. However, these require the ability to identify
OA at a stage when it is potentially reversible, and detect small
changes in cartilage structure and function to enable treatment
efficacy to be evaluated within an acceptable timeframe. This has
not been possible using conventional imaging techniques but recent
advances in musculoskeletal imaging have been significant. In this
review we discuss the role of different imaging modalities in the
diagnosis of the earliest changes of OA. The increasing number of
MRI sequences that are able to non-invasively detect biochemical
changes in cartilage that precede structural damage may offer a
great advance in the diagnosis and treatment of this debilitating
condition. Cite this article:
