Molecular Determinants of Melatonin Signaling Dysfunction in Adolescent Idiopathic Scoliosis

Azeddine, Bouziane; Letellier, Kareen; Wang, Da Shen; Moldovan, Florina; Moreau, Alain

doi:10.1097/blo.0b013e31811f39fa

Cited by 83 publications

(77 citation statements)

References 28 publications

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“…However, polymorphisms in melatonin receptor 1B have been associated with the occurrence of idiopathic scoliosis [46,47]. Furthermore, it has been demonstrated that melatonin stimulation of AIS osteoblasts results in differential phosphorylation of the G inhibitory signalling proteins that are coupled to the melatonin receptors, compared with normal osteoblasts [3].…”

Section: Intrinsic Factors Of the Ais Spinal Musculoskeletal System Smentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

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Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

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Section: Intrinsic Factors Of the Ais Spinal Musculoskeletal System Smentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

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“…However, the etiopathogeny is still unclear, largely due to its multifactorial origin (Weinstein et al, 2008). While a clear genetic basis is lacking so far (Miller, 2007), AIS is correlated in part with abnormal levels of tyrosine, sex and growth hormones, dysfunction of the melatonin-signaling pathway, and calcium-binding receptor protein calmodulin (Ahn et al, 2002;Moreau et al, 2004;Azeddine et al, 2007;Cheung et al, 2008). These biochemical abnormalities, however, might be more related to the progression rather than the origin of AIS (Kindsfater et al, 1994;Machida et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Vestibular Asymmetry as the Cause of Idiopathic Scoliosis: A Possible Answer fromXenopus

Lambert¹,

Malinvaud²,

Glaunès

et al. 2009

J. Neurosci.

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Human idiopathic scoliosis is characterized by severe deformations of the spine and skeleton. The occurrence of vestibular-related deficits in these patients is well established but it is unclear whether a vestibular pathology is the common cause for the scoliotic syndrome and the gaze/posture deficits or if the latter behavioral deficits are a consequence of the scoliotic deformations. A possible vestibular origin was tested in the frog Xenopus laevis by unilateral removal of the labyrinthine endorgans at larval stages. After metamorphosis into young adult frogs, X-ray images and three-dimensional reconstructed micro-computer tomographic scans of the skeleton showed deformations similar to those of scoliotic patients. The skeletal distortions consisted of a curvature of the spine in the frontal and sagittal plane, a transverse rotation along the body axis and substantial deformations of all vertebrae. In terrestrial vertebrates, the initial postural syndrome after unilateral labyrinthectomy recovers over time and requires body weight-supporting limb proprioceptive information. In an aquatic environment, however, this information is absent. Hence, the lesion-induced asymmetric activity in descending spinal pathways and the resulting asymmetric muscular tonus persists. As a consequence the mostly cartilaginous skeleton of the frog tadpoles progressively deforms. Lack of limb proprioceptive signals in an aquatic environment is thus the element, which links the Xenopus model with human scoliosis because a comparable situation occurs during gestation in utero. A permanently imbalanced activity in descending locomotor/posture control pathways might be the common origin for the observed structural and behavioral deficits in humans as in the different animal models of scoliosis.

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“…Thus, it is hypothesized that adjustment of menarche age may contribute to predisposition and curve progression potential of idiopathic scoliosis. In addition, potential difference of menarche age compared with normal control population may be correlated with hormonal disturbance involving estrogen, melatonin, and leptin [5][6][7][8][9][10], thus contributing to abnormal pubertal growth, which may be responsible for curve onset and progression of AIS. Such hypothesis, first and foremost, warrants menstrual status data supportive of abnormal menarche age with respect to general population.…”

Section: Introductionmentioning

confidence: 99%

Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature

et al. 2010

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Age at menarche is closely related to scoliosis progression during adolescence. Current data concerning the timing of menarche between scoliotic and non-scoliotic girls in the literature are conflicting, with inconclusive results. The aim of this study was to investigate the distribution difference of age at menarche for adolescent idiopathic scoliosis (AIS) girls and normal control population and to subsequently elucidate the menarche age difference through literature reviewing. Moreover, menarche age of AIS girls with Cobb angle \40°, 40-60°, [60°were compared to estimate its association with curve severity. Menstrual status data were available for 6,376 healthy female adolescents and 2,196 AIS girls. We notice that less than 10% of healthy Chinese girls experienced onset of menses before 11.38 years, and approximately 90% of healthy Chinese girls were menstruating by 13.88 years, with a median age of 12.63 years. As for AIS girls, less than 10% started to menstruate before 11.27 years, and approximately 90% were menstruating by 14.38 years, with a median age of 12.83 years. Average menarche age in AIS (12.83 ± 1.22 years) was significantly later than that of normal control girls (12.63 ± 0.98 years) (p \ 0.001). Age at menarche for AIS affected girls was significantly greater than that of normal control girls at 75%, 90% of whom had attained menarche (p = 0.001, p \ 0.001). Proportion of girls starting to menstruate after 14 years was significantly higher in AIS population compared with normal controls (16.3 vs. 8.1%, p \ 0.001). In addition, AIS girls with Cobb angle [60°experienced onset of menses at an average age of 13.25 years, which was significantly later than AIS girls with Cobb angle \40°(12.81 years, p \ 0.05) and marginally significantly later than AIS girls with Cobb angle between 40 and 60°(12.86 years, p = 0.053). In conclusion, a tendency of delayed onset of menarche was observed in Chinese idiopathic scoliotic girls in this large sample study, especially for girls with Cobb angle [60°, which is supported by multiple previously established positive linkages on AIS etiology studies. Accordingly it is believed that late menarche may contribute importantly to abnormal pubertal growth and subsequently modulate curve behavior in AIS.

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Molecular Determinants of Melatonin Signaling Dysfunction in Adolescent Idiopathic Scoliosis

Cited by 83 publications

References 28 publications

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Vestibular Asymmetry as the Cause of Idiopathic Scoliosis: A Possible Answer fromXenopus

Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature

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