Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin.
Melatonin deficiency has been postulated as an etiologic factors in adolescent idiopathic scoliosis (AIS). In previous studies, melatonin was shown to regulate skeletal growth and bone formation in both humans and rats. Although it remains controversial whether there are differences in serum melatonin level between AIS and control subjects, melatonin signaling pathway dysfunction in osteoblasts has been reported in patients with AIS. Recently, our group found that melatonin receptor 1B (MT2) gene polymorphism was associated with the occurrence of AIS. Hence, the present study investigated the effect of melatonin on AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 17 severe AIS girls and nine control subjects. The osteoblasts were exposed to different concentrations of melatonin for 3 days. The effects of melatonin on cell proliferation (as evidenced by MTT assay) and differentiation (demonstrated by alkaline phosphatase activity) were determined. In the control group, melatonin significantly stimulated osteoblasts to proliferate and differentiate. However, in the AIS group, the stimulatory effects of melatonin were not discernible. Importantly, this finding demonstrated that there is a significant difference between AIS and control osteoblasts in functional response toward melatonin. Melatonin-stimulated proliferation of control osteoblasts was inhibited by the MT2 antagonist, 4-phenyl-2-propionamidotetraline, as well as by luzindole, a nonselective melatonin receptor antagonist, suggesting that MT2 is associated with the proliferative action of melatonin. The lack of response in AIS osteoblasts might be because of dysfunction of the melatonin signaling pathway, which may contribute to the low bone mineral density and abnormal skeletal growth observed in patients with AIS.
Man
Gene Chi-Wai
GC
Faculty of Medicine, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Wang
William Wei-Jun
WW
Yeung
Benson Hiu-Yan
BH
Lee
Simon Kwong-Man
SK
Ng
Bobby Kin-Ah
BK
Hung
Wing-Yin
WY
Wong
Jack Ho
JH
Ng
Tzi-Bun
TB
Qiu
Yong
Y
Cheng
Jack Chun-Yiu
JC
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology*; D010784:Photomicrography; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors; D012600:Scoliosis / Q000473:pathology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
C114459:4-phenyl-2-propionamidotetraline; D044123:Receptor, Melatonin, MT2; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C057154:luzindole; D000469:Alkaline Phosphatase; D008550:Melatonin