Enhanced expression of the central survival of motor neuron (SMN) protein during the pathogenesis of osteoarthritis.
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.
Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar, Germany.
Magali
M
Cucchiarini
Henning
H
Madry
Ernest F
EF
Terwilliger
D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011817:Rabbits; D012720:Severity of Illness Index; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D053583:Interleukin-1beta; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D014409:Tumor Necrosis Factor-alpha
SMN expression; osteoarthritis progression; pro-inflammatory cytokines