Introduction: We hypothesized that scoliosis development in patients with idiopathic scoliosis (IS) and different melatonin‐deficient animal models could be induced by a similar mechanism involving a common downstream effector regulated by melatonin. Indeed, the study of the molecular changes occurring in pinealectomized chickens revealed an increased production of OPN, at the mRNA and protein levels, in paraspinal muscles of scoliotic chickens. Therefore, we investigated the involvement of OPN, a multifunctional cytokine, in IS pathomechanism.
Methods: A group of 320 consecutive patients with IS were compared with 120 healthy control subjects and 82 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 enzymelinked immunosorbent assays. Contributions of OPN and CD44 receptors to idiopathic scoliosis were validated using C57BI/6j mice, a well known scoliosis animal model.
Results: Mean plasma OPN levels were significantly increased in IS patients and correlated with disease severity, with average values of 743±326 ng/ml and 975±389 ng/ml for moderate (10–44 degree) and severe (≥ 45 degree) spinal deformities, respectively, when compared to the healthy control group (568±216 ng/ml). Elevated plasma OPN levels were also found in the asymptomatic at‐risk group (871 ±387 ng/ ml), suggesting that these changes precede scoliosis onset. Mean plasma sCD44 levels were significantly lower only in IS patients with Cobb angle ≥ 45 degree compared to healthy control subjects. All transgenic C57B1/6j mice devoid of OPN or CD44 receptor were protected against scoliosis, contrasting with wild‐type ones.
Conclusion: 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.
Significance: Plasma OPN and sCD44 values could be useful markers for diagnosis of IS and prognosis of curve progression.