Abnormal melatonin receptor 1B expression in osteoblasts from girls with adolescent idiopathic scoliosis.

Melatonin signaling dysfunction has been associated with the etiology of adolescent idiopathic scoliosis (AIS). Genetic analysis has also associated the occurrence of AIS with the MT2 gene. Thus, we determined whether there is abnormality in the protein expression of melatonin receptors (MT) in AIS osteoblasts. In this study, we recruited 11 girls with severe AIS and eight normal subjects for intraoperative bone biopsies. MT1 and MT2 receptor protein expressions in the isolated osteoblasts were detected. Also, cell proliferation assay using different melatonin concentrations (0, 10(-9), 10(-5), 10(-4) m) was carried out. The results showed that both MT1 and MT2 receptors are expressed in osteoblasts of the controls. While MT1 receptors were expressed in osteoblasts of all AIS subjects, osteoblasts of only 7 of 11 AIS showed expression of MT2 receptors. Melatonin stimulated control osteoblasts to proliferate. However, proliferation of AIS osteoblasts without expression of MT2 receptor, after treatment with melatonin, was minimal when compared with control and AIS osteoblasts with MT2 receptor expression. The proliferation of AIS osteoblasts with MT2 receptor was greater than those without. This is the first report demonstrating a difference between AIS and normal osteoblasts in the protein expression of MT2 receptor. The results suggest that there is a possible functional effect of MT2 receptor on osteoblast proliferation. AIS osteoblasts without expression of MT2 receptor showed the lowest percentage of viable cells after melatonin treatment. This possibly indicates the modulating role of melatonin through MT2 receptor on the proliferation of osteoblasts.

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.

Correlation of Risser sign, radiographs of hand and wrist with the histological grade of iliac crest apophysis in girls with adolescent idiopathic scoliosis.

STUDY DESIGN: A correlation analysis between histologic grade (HG) of iliac crest apophysis and skeletal age assessments. OBJECTIVE: To study the correlation between HGs of iliac crest apophysis and the skeletal age of hand and wrist, digital skeletal age (DSA), and Risser sign in the girls with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The evaluation of the remaining growth of the patients clinically and radiologically is highly significant in predicting the curve progression and thus influencing the treatment strategy in AIS. METHODS: Fifty-three AIS girls with a mean age of 14.0 years undergoing corrective posterior spinal surgery and instrumentation with autogenous bone graft were recruited. Menarche status was recorded while the skeletal age of hand and wrist, DSA, and Risser grade were evaluated radiologically. Using a standardized HG of proliferative chondrocyte zone of the iliac crest apophysis, correlation between the HGs and the radiologic and clinical skeletal maturity parameters was analyzed. RESULTS: The HGs were negatively correlated with the radiologic parameters with the highest correlation coefficient between HGs and skeletal age of hand and wrist. The negative correlation between HGs and the 2 clinical parameters was significant and could be enhanced by combining with the radiologic parameters. No proliferative chondrocyte zone of the apophysis was detected when patients were either over 16 years of skeletal age or Risser grade 5, as well as 2-year postmenarche or over 15 years of chronological age in patients with DSA stage III and Risser grade 4. CONCLUSION: Radiologic skeletal age of the wrist and digits can provide important information for maturity assessment in girls with AIS. It can also enhance the sensitivity of clinical parameters in determining the remaining growth potential.