Introduction: The study of the molecular changes occurring in scoliosis animal models revealed an increased production of Osteopontin (OPN), at the mRNA and protein levels and led us to study the role of this multifunctional cytokine in idiopathic scoliosis (IS) pathomechanism.
Methods: A group of 434 consecutive patients with IS were compared with 247 healthy control subjects and 121 asymptomatic offspring, born from at least one scoliotic parent, who are considered at-risk of developing this disorder. Plasma OPN and soluble CD44 receptor (sCD44) levels were measured by enzyme-linked immunosorbent assays.
Results: Mean plasma OPN levels were significantly increased in IS patients and correlated with disease severity, with average values of 712±299 ng/ml and 914±366 ng/ml for moderate (10–44°) and severe (geq45°) spinal deformities, respectively, when compared to the healthy control group (540±244 ng/ml). Elevated plasma OPN levels were also found in the asymptomatic at-risk group (816±349 ng/ml), suggesting that these changes precede scoliosis onset. Mean plasma sCD44 levels were significantly lower only in IS patients with Cobb angle ≥45° compared to healthy control subjects. All transgenic C57Bl/6j mice devoid of OPN were protected against scoliosis, contrasting with wild-type ones.
Conclusions: Our clinical data and experiments on animals demonstrate that OPN is essential to induce scoliosis formation and curve progression through interactions with CD44 receptors, thus offering a first molecular concept to explain the pathomechanism leading to the asymmetrical growth of the spine in idiopathic scoliosis. Plasma OPN and sCD44 values could be useful markers for diagnosis of IS and prognosis of curve progression.