Scoliosis Clinical Trial
Official title:
Ghrelin Cellular Resistance Study 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.
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