Leptin has been suggested to play a role in the etiology of Adolescent 
Idiopathic Scoliosis (AIS), however, the leptin levels in AIS girls are still a 
discrepancy, and no in vitro study of leptin in AIS is reported. We took a 
series of case-control studies, trying to understand whether Leptin gene 
polymorphisms are involved in the etiology of the AIS or the change in leptin 
level is a secondary event, to assess the level of leptin receptor, and to 
evaluate the differences of response to leptin between AIS cases and controls. 
We screened all exons of Leptin gene in 45 cases and 45 controls and selected 
six tag SNPs to cover all the observed variations. Association analysis in 446 
AIS patients and 550 healthy controls showed no association between the 
polymorphisms of Leptin gene and susceptibility/severity to AIS. Moreover, 
adipogenesis assay of bone mesenchymal stem cells (MSCs) suggested that the 
adipogenic ability of MSCs from AIS girls was lower than controls. After 
adjusting the differentiation rate, expressions of leptin and leptin receptor 
were similar between two groups. Meanwhile, osteogenesis assay of MSC showed the 
leptin level was similar after adjusting the differentiation rate, but the 
leptin receptor level was decreased in induced AIS osteoblasts. 
Immunocytochemistry and western blot analysis showed less leptin receptors 
expressed in AIS group. Furthermore, factorial designed studies with 
adipogenesis and osteogenesis revealed that the MSCs from patients have no 
response to leptin treatment. Our results suggested that Leptin gene variations 
are not associated with AIS and low serum leptin probably is a secondary outcome 
which may be related to the low capability of adipogenesis in AIS. The decreased 
leptin receptor levels may lead to the hyposensitivity to leptin. These findings 
implied that abnormal peripheral leptin signaling plays an important role in the 
pathological mechanism of AIS.