Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice.

Osteoarthritis induced by destabilization of the medial meniscus is reduced in germ-free mice.
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DOI:
10.1016/j.joca.2018.05.016
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发表时间:
2018-08
影响因子:
7
通讯作者:
Loeser RF
Loeser RF
中科院分区:
医学2区
文献类型:
--
作者:
Ulici V;Kelley KL;Azcarate-Peril MA;Cleveland RJ;Sartor RB;Schwartz TA;Loeser RF

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确定肠道微生物群对损伤引起的骨关节炎 (OA) 发展的贡献。使用不稳定的内侧半月板 (DMM) 模型诱导 20 只无菌 (GF) C57BL/6J 雄性小鼠饲养在无菌设施中,以及 23 只品系匹配的无特定病原体 (SPF) 小鼠,分为 2 个年龄组 -13.5 周(DMM 平均年龄(17 SPF 和 15 GF))和 43 周平均年龄(6 SPF 和 5 GF)。使用关节软骨结构 (ACS)、番红 O (SafO) 染色缺失、骨赘大小和滑膜增生评分来测量 OA 严重程度。通过 16S rRNA 扩增子测序对粪便样本进行微生物组分析,并测量血浆中的 LPS 和 LPS 结合蛋白 (LBP)。与 SPF DMM 小鼠相比,GF DMM 小鼠每个关节的最大 (MAX) ACS 评分降低了 28% (p = 0.036),而每个关节评估的所有切片的 SafO 总评分降低了 31% (p = 0.009)。当分析中只包括较年轻的小鼠时,SPF 和 GF 小鼠在这些分数上的差异更大。年轻的 GF DMM 小鼠的骨赘大小(36%,P = 0.0119)和 LBP(27%,P = 0.007)也显着减少,但滑膜评分或 LPS 没有显着减少。在具有高和低最大 ACS 分数的 SPF 小鼠之间注意到许多操作分类单元 (OTU) 的相对丰度存在差异。这些结果表明,与肠道微生物群相关的因素促进了关节损伤后 OA 的发展。
To determine the contribution of the gut microbiota to the development of injury-induced osteoarthritis (OA). OA was induced using the destabilized medial meniscus (DMM) model in 20 germ-free (GF) C57BL/6J male mice housed in a gnotobiotic facility and 23 strain-matched specific pathogen free (SPF) mice in 2 age groups −13.5 weeks avg age at DMM (17 SPF and 15 GF) and 43 weeks avg age at DMM (6 SPF and 5 GF). OA severity was measured using scores for articular cartilage structure (ACS), loss of safranin O (SafO) staining, osteophyte size, and synovial hyperplasia. Microbiome analysis by 16S rRNA amplicon sequencing was performed on stool samples and LPS and LPS binding protein (LBP) were measured in plasma. Compared to the SPF DMM mice, the maximum (MAX) ACS score per joint was 28% lower (p = 0.036) in GF DMM mice while the SafO sum score of all sections evaluated per joint was decreased by 31% (p = 0.009). The differences between SPF and GF mice in these scores were greater when only the younger mice were included in the analysis. The younger GF DMM mice also had significant reductions in osteophyte size (36%, P = 0.0119) and LBP (27%, P = 0.007) but not synovial scores or LPS. Differences in relative abundance of a number of Operational Taxonomic Units (OTUs) were noted between SPF mice with high vs low maximum ACS scores. These results suggest factors related to the gut microbiota promote the development of OA after joint injury.
微生物,肠道和强直性脊柱炎。
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