title: [Etiopathogenesis of adolescent idiopathic scoliosis and new molecular concepts].
abstract: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis that affects a significant number of young teenagers, mainly females (0.2-6 % of the population). Historically, several hypothesis were postulated to explain the aetiology of AIS, including genetic factors, biochemical factors, mechanics, neurological, muscular factors and hormonal factors. The neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS has generated great interest. This hypothesis stems from the fact that experimental pinealectomy in chicken, and more recently in rats maintained in a bipedal mode, produces a scoliosis. The biological relevance of melatonin in idiopathic scoliosis is controversial since no significant decrease in circulating melatonin level has been observed in a majority of studies. Analysis of melatonin signal transduction in musculoskeletal tissues of AIS patients demonstrated for the first time a defect occurring in a cell autonomous manner in different cell types isolated from AIS patients suffering of the most severe form of that disease. These results have led to a classification of AIS patients in three different functional groups depending on their response to melatonin, suggesting that the cause of AIS involves several genes. Molecular analysis showed that melatonin signaling dysfunction is triggered by an increased phosphorylation of Gi proteins inactivating their function. This discovery has led to development of a first scoliosis screening assay. This test, using blood sample, is currently in clinical validation process in Canada and could be used for screening children at high risk of developing AIS.
authors.affiliation: Centre de recherche, CHU Sainte-Justine, Laboratoires de Génétique Moléculaire et de Biologie Cellulaire et Tissulaire des Maladies Musculo-Squelettiques, 3175, chemin de la Côte-Ste-Catherine, Montréal (Québec), H3T 1C5 Canada.
authors.forename: Kareen
authors.initials: K
authors.lastname: Letellier
authors.forename: Bouziane
authors.initials: B
authors.lastname: Azeddine
authors.forename: Sacha
authors.initials: S
authors.lastname: Blain
authors.forename: Isabelle
authors.initials: I
authors.lastname: Turgeon
authors.forename: Da Shen
authors.initials: da S
authors.lastname: Wang
authors.forename: Mamadou Samba
authors.initials: MS
authors.lastname: Boiro
authors.forename: Florina
authors.initials: F
authors.lastname: Moldovan
authors.forename: Hubert
authors.initials: H
authors.lastname: Labelle
authors.forename: Benoît
authors.initials: B
authors.lastname: Poitras
authors.forename: Charles-Hilaire
authors.initials: CH
authors.lastname: Rivard
authors.forename: Guy
authors.initials: G
authors.lastname: Grimard
authors.forename: Stefan
authors.initials: S
authors.lastname: Parent
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.forename: Ginette
authors.initials: G
authors.lastname: Lacroix
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
mesh_terms: D000293:Adolescent; D001842:Bone and Bones / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009490:Neurosecretory Systems / Q000503:physiopathology; D012600:Scoliosis / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D012744:Sex Ratio