Ghrelin Resistance in Adolescents With Idiopathic Scoliosis

Adolescent idiopathic Scoliosis (AIS) is the most common spine pathology. It is opposed to secondary scoliosis due to chronic diseases. Many hypotheses have been made to elucidate the origin of this illness. Recently, the melatonin pathway has been investigated as pinealectomy of the chicken creates a scoliosis that resembles AIS and melatonin supplementation reverses the process. In addition administration of melatonin to AIS patients improved the pathology. However this hypothesis has shown controversial results. Recent studies have demonstrated melatonin cellular resistance in osteoblastic cells from AIS patients. Melatonin acts through G protein coupled receptor (GPCR), mainly using the Gi pathway. In AIS osteoblasts, this pathway is blocked leading to a decrease in the inactivation of the adenylyl cyclase and therefore maintenance of high level of cyclic adenosine monophosphate (cAMP) concentrations in the cells. As modulation of cAMP is important for osteogenesis such resistance may be critical for the initiation or the development of AIS.

Gi signalization is used by several other GPCR, thus, this hormonal resistance could logically be found in other hormonal or mediator pathways. A precedent study previously focused on ghrelin in AIS, and demonstrated that AIS patients possess elevated plasmatic values of ghrelin. This study also observed decreased response to ghrelin in AIS cultures osteoblasts.