Normal leptin expression, lower adipogenic ability, decreased leptin receptor and hyposensitivity to Leptin in Adolescent Idiopathic Scoliosis.
Normal leptin expression, lower adipogenic ability, decreased leptin receptor and hyposensitivity to Leptin in Adolescent Idiopathic Scoliosis.
复制标题
青少年特发性脊柱侧凸的瘦素表达正常、成脂能力降低、瘦素受体减少和对瘦素不敏感
DOI：
10.1371/journal.pone.0036648
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang D
中科院分区：
文献类型：
--
作者：
Liang G;Gao W;Liang A;Ye W;Peng Y;Zhang L;Sharma S;Su P;Huang D
瘦素已被认为在青少年特发性脊柱侧凸（AIS）的病因学中发挥作用，然而，AIS女孩的瘦素水平仍然存在差异，并且没有关于AIS中瘦素的体外研究报道。我们进行了一系列的病例对照研究，试图了解瘦素基因多态性是否参与AIS的病因学，或者瘦素水平的变化是次要事件，评估瘦素受体水平，并评估AIS病例与对照组对瘦素的反应差异。我们筛选了45例病例和45例对照的Leptin基因的所有外显子，并选择了6个标签snp来覆盖所有观察到的变异。对446名AIS患者和550名健康对照者的关联分析显示，瘦素基因多态性与AIS易感性/严重程度之间没有关联。此外，骨间充质干细胞（MSCs）的成脂实验表明，来自AIS女孩的MSCs的成脂能力低于对照组。调整分化率后，两组间瘦素及瘦素受体表达相似。同时，MSC成骨实验显示，调整分化率后，其瘦素水平相近，但诱导AIS成骨细胞的瘦素受体水平降低。免疫细胞化学和western blot分析显示AIS组瘦素受体表达减少。此外，脂肪生成和成骨的因子设计研究显示，来自患者的间充质干细胞对瘦素治疗没有反应。我们的研究结果表明，瘦素基因变异与AIS无关，低血清瘦素可能是AIS的次要结局，可能与AIS的低脂肪生成能力有关。瘦素受体水平降低可能导致对瘦素的低敏感性。提示外周瘦素信号异常在AIS的病理机制中起重要作用。
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.
登录
查看更多内容
影响因子：
6.2
作者：
Baldock, Paul A.;Allison, Susan;Herzog, Herbert
通讯作者：
Herzog, Herbert
影响因子：
7.4
作者：
Dardeno, Tina A.;Chou, Sharon H.;Moon, Hyun-Seuk;Chamberland, John P.;Fiorenza, Christina G.;Mantzoros, Christos S.
通讯作者：
Mantzoros, Christos S.
影响因子：
3
作者：
Morocz, Monika;Czibula, Agnes;Illes, Tamas
通讯作者：
Illes, Tamas
DOI：
10.1002/bdrc.20197
发表时间：
2011-03
期刊：
Birth defects research. Part C, Embryo today : reviews
影响因子：
--
作者：
Janesick A;Blumberg B
通讯作者：
Blumberg B
影响因子：
6.2
作者：
Bartell, Shoshana M.;Rayalam, Srujana;Baile, Clifton A.
通讯作者：
Baile, Clifton A.