Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2

Yim, Annie P Y; Yeung, H.Y.; Sun, Guang-quan; Lee, Kwong-man; Ng, T.B.; Lam, TP; Ng, Benjamin; Qiu, Yong; Moreau, Alain; Cheng, Jack C. Y.

doi:10.3390/ijms14036345

Cited by 20 publications

(12 citation statements)

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“…In osteoblasts from girls with AIS, an abnormal expression of MT2 receptor has been observed, and the expression was not demonstrable in four out of the eleven girls [ 25 ]. Furthermore, AIS patients with a low level of expression of MT2 receptor in osteoblasts showed a longer arm span than those with a normal expression level of MT2 receptor [ 34 ]. Hence, a comprehensive investigation on the MT2 receptor including the expression of RNA and protein, the structure of DNA and protein, and the coupling between MT2 receptor and Gi/Gs proteins should be carried out in GPCs from AIS subjects and control subjects to facilitate further understanding of the abnormalities in the MT2 receptor.…”

Section: Resultsmentioning

confidence: 99%

“…Man et al [ 24 ] noted that melatonin failed to promote both proliferation and differentiation of osteoblasts from AIS subjects, which might contribute to the low bone mineral density in these patients [ 41 , 42 , 43 , 44 ]. This abnormality of melatonin could be attributed to the abnormal expression of MT2 receptor [ 25 , 34 ]. Taking these observations together, it is likely that melatonin signaling pathway dysfunction could be a systemic problem and plays an important role in the abnormal systemic bone growth in AIS subjects [ 4 , 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

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Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis

Wang

Man

Wong

et al. 2014

IJMS

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Abnormalities in the melatonin signaling pathway and the involvement of melatonin receptor MT2 have been reported in patients with adolescent idiopathic scoliosis (AIS). Whether these abnormalities were involved in the systemic abnormal skeletal growth in AIS during the peripubertal period remain unknown. In this cross-sectional case-control study, growth plate chondrocytes (GPCs) were cultured from twenty AIS and ten normal control subjects. Although the MT2 receptor was identified in GPCs from both AIS and controls, its mRNA expression was significantly lower in AIS patients than the controls. GPCs were cultured in the presence of either the vehicle or various concentrations of melatonin, with or without the selective MT2 melatonin receptor antagonist 4-P-PDOT (10 µM). Then the cell viability and the mRNA expression of collagen type X (COLX) and alkaline phosphatase (ALP) were assessed by MTT and qPCR, respectively. In the control GPCs, melatonin at the concentrations of 1, 100 nM and 10 µM significantly reduced the population of viable cells, and the mRNA level of COLX and ALP compared to the vehicle. Similar changes were not observed in the presence of 4-P-PDOT. Further, neither proliferation nor differentiation of GPCs from AIS patients was affected by the melatonin treatment. These findings support the presence of a functional abnormality of the melatonin signaling pathway in AIS GPCs, which might be associated with the abnormal endochondral ossification in AIS patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis

Wang

Man

Wong

et al. 2014

IJMS

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“…These same genes play an essential role in regulating osteoblastogenesis and osteoblast function, bone mineralization, and ossification . In keeping with this, a disruption in melatonin‐mediated signaling, whether it be through a suppression of nocturnal melatonin levels by light at night (LAN) or through impaired melatonin receptor signaling in osteoblasts, is thought to underlie, respectively, the increased risk of hip and wrist fracture and low BMD in shift workers and to the development of adolescent idiopathic scoliosis . Decreases in melatonin have been shown to alter bone morphology in various models including fish , chickens , and mice .…”

Section: Melatonin and Bonementioning

confidence: 99%

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures

Maria

Witt‐Enderby

2014

Journal of Pineal Research

164

159

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An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin's role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and osteoprotegerin synthesis and release from osteoblasts, can induce osteoblastogenesis while inhibiting osteoclastogenesis. Also, melatonin's free-radical scavenging and antioxidant properties of this indoleamine are discussed as yet an additional mechanism by which melatonin can maintain one's bone health, especially oral health. The clinical use for melatonin in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease is discussed. ; the female-to-male ratio for fracture is 1.6 [1]. In the European Union, approximately 22 million women and 5.5 million men (between 50 and 84 yr) are projected to have osteoporosis; this number will rise by 23% by 2025 [3]. In the United States, nearly 57 million adults over age 50 are affected by bone disease, 48 million adults have osteopenia, and 9 million adults have osteoporosis, which places these individuals at risk for developing bone fracture. If left unchanged, by 2030, the prevalence of osteoporosis will increase to 11.9 million and 64.3 million with osteopenia [4].In the United States, the annual fracture rate is 1.5 million per year (300,000 hip and 700,000 vertebral fractures), which is expected to increase by 3 million by 2025 [5,6]. In the United Kingdom, although it was expected that the 12-month survival rate after hip fracture would be 90-91%, the actual numbers were less than expected with 63.3% of men and 74.9% of women surviving [7]. In the United States, hip fracture is responsible for approximately 31,000 excess deaths within 6 months, which can start as early as age 50; this is significant, considering that one in every three women and one in five men in the United States will experience an osteoporosis-related fracture in their lifetime [6]. In addition to increasing morbidity and mortality rates, osteoporosis-related fractures are also creating huge economical burdens to societies worldwide. For example, osteoporosis treatment and related fracture cost in the United States (per year) is $19 billion, which is expected to increase to $25.3 billion by 2025 [6]. In 2010, osteoporosis-related costs amounted ...

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“…The increase in bone mass was also observed after administration of melatonin in vivo [ 65 , 66 , 67 ]. In our studies, it was found that osteoblasts cultured from human AIS patients failed to respond normally to melatonin challenge at various doses with regard to proliferation and differentiation [ 68 , 69 , 70 ] in contrast to that of the normal controls. Despite this well-known clinical manifestation of AIS, its pathogenesis and relationship to premature osteoporosis remain unresolved.…”

Section: Discussionmentioning

confidence: 90%

A Review of Pinealectomy-Induced Melatonin-Deficient Animal Models for the Study of Etiopathogenesis of Adolescent Idiopathic Scoliosis

Man

Wang

Yim

et al. 2014

IJMS

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Adolescent idiopathic scoliosis (AIS) is a common orthopedic disorder of unknown etiology and pathogenesis. Melatonin and melatonin pathway dysfunction has been widely suspected to play an important role in the pathogenesis. Many different types of animal models have been developed to induce experimental scoliosis mimicking the pathoanatomical features of idiopathic scoliosis in human. The scoliosis deformity was believed to be induced by pinealectomy and mediated through the resulting melatonin-deficiency. However, the lack of upright mechanical spinal loading and inherent rotational instability of the curvature render the similarity of these models to the human counterparts questionable. Different concerns have been raised challenging the scientific validity and limitations of each model. The objectives of this review follow the logical need to re-examine and compare the relevance and appropriateness of each of the animal models that have been used for studying the etiopathogenesis of adolescent idiopathic scoliosis in human in the past 15 to 20 years.

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Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2

Cited by 20 publications

References 63 publications

Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis

Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures

A Review of Pinealectomy-Induced Melatonin-Deficient Animal Models for the Study of Etiopathogenesis of Adolescent Idiopathic Scoliosis

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