Chemokine expression is upregulated in chondrocytes in diabetic fracture healing.
Chemokine expression is upregulated in chondrocytes in diabetic fracture healing.
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DOI：
10.1016/j.bone.2012.12.006
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发表时间：
2013-03
期刊：
影响因子：
4.1
通讯作者：
Graves DT
中科院分区：
文献类型：
--
作者：
Alblowi J;Tian C;Siqueira MF;Kayal RA;McKenzie E;Behl Y;Gerstenfeld L;Einhorn TA;Graves DT
趋化因子被认为在骨代谢的几个方面起重要作用，包括白细胞的募集和破骨细胞的形成。我们研究了糖尿病对正常和糖尿病骨折愈合中趋化因子表达的影响。在链脲佐菌素诱导的糖尿病小鼠和匹配的血糖正常对照小鼠中进行股骨骨折。进行微阵列分析并评估体内趋化因子mRNA水平。通过免疫组化检测骨折骨痂中的CCL 4，并通过用TNF特异性抑制剂pegsunercept治疗动物来研究TNF在糖尿病增强表达中的作用。用ATDC 5软骨细胞进行体外研究。糖尿病显著上调体内几种趋化因子的mRNA水平，包括CCL 4、CCL 8、CCL 6、CCL 11、CCL 20、CCL 24、CXCL 2、CXCL 5和趋化因子受体CCR 5和CXCR 4。软骨细胞是CCL 4的重要来源，其在糖尿病骨折中的表达依赖于糖尿病骨折中的TNF（P<0.05）。TNF-α能显著增加FOXO 1 siRNA敲除的几种趋化因子的mRNA表达（P<0.05）。FOXO 1过表达诱导CCL 4在mRNA和蛋白水平的表达，FOXO 1敲低则降低CCL 4的表达。目前的研究指出TNF-α作为糖尿病增强软骨细胞趋化因子表达的机制的重要性，这可能有助于在糖尿病骨折愈合中观察到的软骨加速损失。此外，体外结果表明FOXO 1是介导这种效应的潜在重要转录因子。
Chemokines are thought to play an important role in several aspects of bone metabolism including the recruitment of leukocytes and the formation of osteoclasts. We investigated the impact of diabetes on chemokine expression in normal and diabetic fracture healing. Fracture of the femur was performed in streptozotocin-induced diabetic and matched normoglycemic control mice. Microarray analysis was carried out and chemokine mRNA levels in vivo were assessed. CCL4 were examined in fracture calluses by immunohistochemistry and the role of TNF in diabetes-enhanced expression was investigated by treatment of animals with the TNF-specific inhibitor, pegsunercept. In vitro studies were conducted with ATDC5 chondrocytes. Diabetes significantly upregulated mRNA levels of several chemokines in vivo including CCL4, CCL8, CCL6, CCL11, CCL20, CCL24, CXCL2, CXCL5 and chemokine receptors CCR5 and CXCR4. Chondrocytes were identified as a significant source of CCL4 and its expression in diabetic fractures was dependent on TNF in diabetic fractures (P<0.05). TNF-α significantly increased mRNA levels of several chemokines in vitro which were knocked down with FOXO1 siRNA (P<0.05). CCL4 expression at the mRNA and proteins levels was induced by FOXO1 over-expression and reduced by FOXO1 knockdown. The current studies point to the importance of TNF-α as a mechanism for diabetes enhanced chemokine expression by chondrocytes, which may contribute to the accelerated loss of cartilage observed in diabetic fracture healing. Moreover, in vitro results point to FOXO1 as a potentially important transcription factor in mediating this effect.
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影响因子：
7
作者：
Sandell, L. J.;Xing, X.;Patra, D.
通讯作者：
Patra, D.
影响因子：
11.2
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影响因子：
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影响因子：
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