Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.
Treatment of collagenase-induced osteoarthritis with a viral vector encoding TSG-6 results in ectopic bone formation.
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DOI：
10.7717/peerj.4771
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发表时间：
2018
期刊：
影响因子：
2.7
通讯作者：
van de Loo FAJ
中科院分区：
文献类型：
--
作者：
Broeren MGA;Di Ceglie I;Bennink MB;van Lent PLEM;van den Berg WB;Koenders MI;Blaney Davidson EN;van der Kraan PM;van de Loo FAJ
肿瘤坏死因子诱导基因6（TSG-6）在炎症性关节炎小鼠模型中具有抗炎和软骨保护作用。因为在骨关节炎（OA）中也观察到软骨损伤和炎症，所以我们确定了TSG-6的病毒过表达在实验性骨关节炎中的作用。在重组TSG-6存在下或用慢病毒TSG-6表达载体转导后，骨髓来源的细胞分化为多核破骨细胞。抗酒石酸酸性磷酸酶染色后分析多核破骨细胞，并在牙本质切片上测定吸收活性。在关节内注射腺病毒TSG-6或对照荧光素酶表达载体后，在C57 BL/6小鼠中诱导胶原酶诱导的骨关节炎（CIOA）。使用生物发光Prosense探针测量炎症相关蛋白酶活性。在第二次腺病毒注射后，在用番红-O染色的组织切片中评估软骨损伤。异位骨形成评分的X线图像的受影响的膝盖。TSG-6不抑制多核破骨细胞的形成，但引起牙本质切片上的吸收活性的显著降低。与荧光素酶对照病毒相比，CIOA中的腺病毒TSG-6基因治疗不能减少软骨损伤，并且在TSG-6和对照治疗组之间没有注意到炎症相关蛋白酶活性的显著差异。相反，X射线分析和组织学分析显示TSG-6治疗组中存在异位骨形成。基于TSG-6表达的基因治疗不能在实验性骨关节炎中提供软骨保护，而是导致异位骨形成增加。
Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector. Multi-nucleated osteoclasts were analyzed after tartrate resistant acid phosphatase staining and resorption activity was determined on dentin slices. Collagenase-induced osteoarthritis (CIOA) was induced in C57BL/6 mice after intra-articular injection of an adenoviral TSG-6 or control luciferase expression vector. Inflammation-related protease activity was measured using bioluminescent Prosense probes. After a second adenovirus injection, cartilage damage was assessed in histological sections stained with Safranin-O. Ectopic bone formation was scored in X-ray images of the affected knees. TSG-6 did not inhibit the formation of multi-nucleated osteoclasts, but caused a significant reduction in the resorption activity on dentin slices. Adenoviral TSG-6 gene therapy in CIOA could not reduce the cartilage damage compared to the luciferase control virus and no significant difference in inflammation-related protease activity was noted between the TSG-6 and control treated group. Instead, X-ray analysis and histological analysis revealed the presence of ectopic bone formation in the TSG-6 treated group. Gene therapy based on the expression of TSG-6 could not provide cartilage protection in experimental osteoarthritis, but instead resulted in increased ectopic bone formation.
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影响因子：
2.3
作者：
Prieto-Potin I;Largo R;Roman-Blas JA;Herrero-Beaumont G;Walsh DA
通讯作者：
Walsh DA
影响因子：
--
作者：
Glant, TT;Kamath, RV;Mikecz, K
通讯作者：
Mikecz, K
影响因子：
4.8
作者：
Lesley, J;Gál, I;Mikecz, K
通讯作者：
Mikecz, K
影响因子：
6
作者：
Meran, Soma;Martin, John;Phillips, Aled
通讯作者：
Phillips, Aled
静脉注射HMSC改善了小鼠的心肌梗塞，因为栓塞在肺中的细胞被激活以分泌抗炎蛋白TSG-6。
影响因子：
23.9
作者：
Lee RH;Pulin AA;Seo MJ;Kota DJ;Ylostalo J;Larson BL;Semprun-Prieto L;Delafontaine P;Prockop DJ
通讯作者：
Prockop DJ