Abstract
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.
Highlights
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine and its etiology remains unknown
There was no significant difference in the proliferation of AIS osteoblasts at any leptin concentration when compared with the untreated group
There were no significant differences in the alkaline phosphatase (ALP) activity of AIS osteoblasts at any leptin concentration when compared with the untreated group
Summary
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine and its etiology remains unknown. We reported an abnormal leptin bioavailability with increased levels of the soluble leptin receptor (sOB-R) in AIS girls[15], which was associated with suboptimal bone qualities including lower volumetric BMD in cortical bone and abnormal trabecular bone micro-architecture attributable to impaired osteoblast activities[16,17]. These results suggested a potential role of leptin in contributing to an abnormal osteoblastic activity in AIS. Further to the clinical observations reported in previous publications, this study aimed to examine the effects of exogenous leptin on proliferation, differentiation, and mineralization in osteoblasts in primary culture isolated from bone biopsies of AIS patients, and to compare the effects with those on their non-AIS counterparts
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