TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover
TXNIP is highly regulated in bone biopsies from patients with endogenous Cushing's syndrome and related to bone turnover
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DOI：
10.1530/eje-11-1082
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Bollerslev, Jens
中科院分区：
文献类型：
--
作者：
Lekva, Tove;Ueland, Thor;Bollerslev, Jens
目的：内源性库欣综合征（CS）患者与长期使用外源性糖皮质激素（GC）的患者一样，具有严重的全身表现，包括继发性骨质疏松和低能量骨折。本研究的目的是探讨TXNIP在骨中的功能作用，重点是成骨细胞（OB）分化和OB介导的破骨细胞的活性和功能在vitro.Design和Methods：9骨活检CS手术治疗前后进行了筛选表达的候选基因。微阵列分析显示，编码TXNIP的基因是上调最多的基因之一。结果：手术治疗后，CS患者骨组织中TXNIP基因表达下调。此外，我们的体内数据表明硫氧还蛋白和TXNIP之间的新的关联。我们的体外研究表明，在OBs中沉默TXNIP之后，分化和骨钙素的表达和分泌增加，以及碱性磷酸酶活性增强。此外，治疗破骨细胞沉默TXNIP OB媒体表现出破骨细胞activity.Conclusions：TXNIP在骨中的表达是高度调节活性CS治疗过程中，并在体外骨细胞中的GC。我们的数据表明，TXNIP可能介导GC对OB功能的一些不利影响，以及通过调节OPG/RANKL比例来调节OB介导的破骨细胞生成。
Objective: Patients with endogenous Cushing's Syndrome (CS), as long-time treated patients with exogenous glucocorticoids (GCs), have severe systemic manifestations including secondary osteoporosis and low-energy fractures. The aim of the present study was to investigate the functional role of TXNIP in bone with focus on osteoblast (OB) differentiation and OB-mediated osteoclast activity and function in vitro.Design and methods: Nine bone biopsies from CS before and after surgical treatment were screened for expressional candidate genes. Microarray analyses revealed that the gene encoding TXNIP ranked among the most upregulated genes. Subsequent in vitro and in vivo studies were performed.Results: We found that TXNIP gene in bone is downregulated in CS following surgical treatment. Furthermore, our in vivo data indicate novel associations between thioredoxin and TXNIP. Our in vitro studies showed that silencing TXNIP in OBs was followed by increased differentiation and expression and secretion of osteocalcin as well as enhanced activity of alkaline phosphatase. Moreover, treating osteoclasts with silenced TXNIP OB media showed an increased osteoclast activity.Conclusions: TXNIP expression in bone is highly regulated during the treatment of active CS, and by GC in bone cells in vitro. Our data indicate that TXNIP may mediate some of the detrimental effects of GC on OB function as well as modulate OB-mediated osteoclastogenesis by regulating the OPG/RANKL ratio.