Abnormal Proliferative Response of Chondrocytes to Melatonin in Girls with Adolescent Idiopathic Scoliosis

Melatonin deficiency has been postulated as one of the etiology of adolescent idiopathic scoliosis (AIS). Although the serum melatonin level showed no difference between AIS and control subjects, melatonin signal pathway dysfunction in osteoblast and lymphocyte have been observed in AIS. Moreover, melatonin receptor 2 (MT2) gene was associated with AIS. Previous reports indicated that AIS girls have abnormal skeletal growth which is related to abnormal endochondral development. The present study is to investigate the effect of melatonin on chondrocyte proliferation in girls with AIS and compare it to normal controls. Chondrocytes from 8 AIS and 6 controls were released by serial enzymatic digestion and culture in defined medium for two weeks. Melatonin receptor expression (MT1 and MT2) in chondrocyte were detected by immunocytochemistry. Subconfluence chondrocytes were treated with different concentrations of melatonin for two days before the cell viability was carried out. Both MT1 and MT2 receptors were detected on the cell membrane of the chondrocytes in AIS and control. Inhibition effect of melatonin on chondrocyte proliferation was found in normal controls. Melatonin showed inhibition effect on chondrocyte proliferation in normal controls but not in AIS. Significant difference were found at high dosage level. The effect of non-responsiveness of the chondrocytes to MLT might have important effect on the bone growth and contribute to the etiopathogenesis of AIS. The lack of response could result from underlying dysfunction of MLT signaling pathway.