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强力霉素可诱导骨修复及 Wnt 信号转导改变。

Doxycycline induces bone repair and changes in Wnt signalling.

机构信息

Faculty of Dentistry, Pharmacy and Nursing, Federal University of Ceará, Fortaleza, Brazil.

Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.

出版信息

Int J Oral Sci. 2017 Sep;9(3):158-166. doi: 10.1038/ijos.2017.28.

DOI:10.1038/ijos.2017.28
PMID:28960195
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5709545/
Abstract

Doxycycline (DOX) exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls (CTL) and DOX-treated (10 and 25 mg·kg) molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining (7th day) revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOX10 group (7th and 14th days) revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOX10 and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOX10 and DOX25 groups on the 7th and 14th days. Wnt-10b-immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf (Dkk)-1 immunostaining was decreased by 63% and 46% in the DOX10 and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOX10 and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt 10b and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.

摘要

多西环素 (DOX) 具有抗炎和 MMP 抑制作用。本研究旨在评估 DOX 对牙槽骨修复的影响。对照组 (CTL) 和 DOX 处理组 (10 和 25mg·kg) 的磨牙被提取,大鼠在 7 或 14 天后处死。上颌骨经过处理,进行组织学和免疫组织化学检测。苏木精-伊红染色 (第 7 天) 显示 CTL 组有炎症,而 DOX 处理后炎症部分逆转。第 14 天,CTL 组出现骨新形成、结缔组织、再上皮化和无炎症浸润。DOX 处理组则表现出完全的再上皮化、组织重塑和几乎没有炎症。天狼星红染色显示,DOX10 组在第 7 天和第 14 天Ⅰ型和Ⅲ型胶原纤维的比例增加,与 CTL 和 DOX25 组相比。DOX10 和 DOX25 组在第 7 天和第 14 天均增加了成骨细胞。然而,在第 7 天和第 14 天,DOX10 和 DOX25 组的破骨细胞较少。Wnt-10b 免疫阳性细胞在 DOX 处理组中分别增加了 130%和 150%,而在 CTL 组中则增加了 70%和 140%。在第 7 天,DOX10 和 DOX25 组的 Dickkopf (Dkk)-1 免疫染色分别减少了 63%和 46%。第 14 天,与 CTL 组相比,DOX10 和 DOX25 组的免疫阳性细胞分别减少了 69%和 42%。通过增加成骨细胞、减少破骨细胞、激活 Wnt 10b 和中和 Dkk,DOX 可能是牙周病骨修复的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1543fc5d38ec/ijos201728f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1c64f495f7e4/ijos201728f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/85235464082c/ijos201728f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/2912fd03e429/ijos201728f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/08afe3b2434d/ijos201728f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/d2473859ef96/ijos201728f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1817832d3e17/ijos201728f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1543fc5d38ec/ijos201728f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1c64f495f7e4/ijos201728f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/85235464082c/ijos201728f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/2912fd03e429/ijos201728f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/08afe3b2434d/ijos201728f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/d2473859ef96/ijos201728f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1817832d3e17/ijos201728f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e9/5709545/1543fc5d38ec/ijos201728f7.jpg

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