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Int. J. Mol. Sci. 2014, 15(9), 17100-17114; doi:10.3390/ijms150917100

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

1
Department of Spine Surgery, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China
2
Department of Orthopaedics and Traumatology, the Chinese University of Hong Kong, Hong Kong, China
3
The Joint Scoliosis Research Center of the Chinese University of Hong Kong–Nanjing University, Hong Kong, China
4
Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China
5
School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China
6
Lee Hysan Clinical Research Laboratory, the Chinese University of Hong Kong, Hong Kong, China
*
Author to whom correspondence should be addressed.
Received: 31 July 2014 / Revised: 2 September 2014 / Accepted: 19 September 2014 / Published: 25 September 2014
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
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Abstract

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. View Full-Text
Keywords: idiopathic scoliosis; melatonin; growth plate; chondrocytes; proliferation; differentiation; MT2 receptor; antagonist; dysfunction idiopathic scoliosis; melatonin; growth plate; chondrocytes; proliferation; differentiation; MT2 receptor; antagonist; dysfunction
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MDPI and ACS Style

Wang, W.W.-J.; Man, G.C.-W.; Wong, J.H.; Ng, T.-B.; Lee, K.-M.; Ng, B.K.-W.; Yeung, H.-Y.; Qiu, Y.; Cheng, J.C.-Y. Abnormal Response of the Proliferation and Differentiation of Growth Plate Chondrocytes to Melatonin in Adolescent Idiopathic Scoliosis. Int. J. Mol. Sci. 2014, 15, 17100-17114.

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