Abstract
The identification of new components implicated in the pathogenesis of osteoarthritis (OA) might improve our understanding of the disease process. Here, we investigated the levels of the survival of motor neuron (SMN) expression in OA cartilage considering the fundamental role of the SMN protein in cell survival and its involvement in other stress-associated pathologies. We report that SMN expression is up-regulated in human OA compared with normal cartilage, showing a strong correlation with the disease severity, a result confirmed in vivo in an experimental model of the disease. We further show that the prominent inflammatory cytokines (IL-1β, TNF-α) are critical inducers of SMN expression. This is in marked contrast with the reported impaired levels of SMN in spinal muscular atrophy, a single inherited neuromuscular disorder characterized by mutations in the smn gene whereas OA is a complex disease with multiple aetiologies. While the precise functions of SMN during OA remain to be elucidated, the conclusions of this study shed light on a novel pathophysiological pathway involved in the progression of OA, potentially offering new targets for therapy.
Highlights
Osteoarthritis (OA) is a degenerative disease of the whole joint [1] that affects millions of people worldwide
As chondrocytes are subjected to various stress stimuli in the OA joint, we investigated the expression profiles of the survival of motor neuron gene in the cartilage during the course of OA in light of the response of the SMN product to stress conditions by accumulation of the molecule in stress granules [18] and its significant role in oxidative stress [18,19,20]
We report that the levels of SMN are up-regulated in human OA compared with normal adult cartilage, showing a strong correlation with the disease severity and an influence of key OA mediators (IL-1b and TNF-a), an observation confirmed by analysing the SMN levels in a model of experimentally induced OA in vivo
Summary
Osteoarthritis (OA) is a degenerative disease of the whole joint [1] that affects millions of people worldwide. Osteoarthritis is mainly characterized by a slow, progressive destruction of major components of the extracellular cartilage matrix, resulting from a disturbed balance of physiological processes in chondrocytes [2], the unique cartilage-forming cells. Several lines of evidence have demonstrated the critical involvement of stress stimuli in the pathogenesis of OA, including mechanical stress (loading), oxidative and biochemical stress Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine Critical advances in the identification of OA-related biomarkers that might allow for rapid and effective early OA diagnosis (and for a potential development of beneficial treatment options) [13, 14], the pathophysiology of this complex disorder is not yet fully understood [15,16,17], showing the need to explore new aspects or a 2013 The Authors.
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