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.

Phytoestrogen-rich herb formula "XLGB" prevents OVX-induced deterioration of musculoskeletal tissues at the hip in old rats.

This study investigated a phytoestrogen-rich herb formula, Xianlinggubao (XLGB) (including genistein 510 microg/g and daidzein 2500 microg/g), concerning prevention of OVX-induced deterioration of musculoskeletal tissues in 11-month-old female Wistar rats, which were randomized into Sham, OVX, and XLGB groups. Daily oral administration of XLGB (250 mg/kg/day) started after OVX for 3 months. mRNA of MHC-I IIa IIb of abductor muscle was determined by RT-PCR. The proximal femoral BMD and geometry, microarchitecture, and mechanical strength were evaluated by pQCT, micro-CT, and compressive testing, respectively. The bone turnover biochemical markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) were evaluated. The results showed that (1) XLGB-treated OVX rats showed no difference compared to the Sham group, whereas OVX induced significant deterioration in variables related to bone density, microarchitecture, and mechanical strength (P < 0.05); (2) biochemical markers showed no difference between sham and XLGB groups as compared with higher bone turnover in OVX rats (P < 0.05); (3) mRNA expression of MHC-I IIa IIb was downregulated in OVX rats but upregulated after XLGB treatment (P < 0.05); and (4) as compared with the OVX group, no uterine hypertrophy was found in XLGB-treated rats. In conclusion, findings of this study suggested that the herbal preparation XLGB was able to prevent OVX-induced deterioration of musculoskeletal tissues at the hip without causing uterine stimulation.