Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model.

Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model.
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DOI:
10.3390/biomedicines10061298
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发表时间:
2022-06-01
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
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--
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为了测试骨关节炎(OA)的益生菌疗法,我们在通过部分内侧骨切除术(PMM)诱导OA后,通过口服管饲法(2×/周)给予嗜酸乳杆菌(LA)。通过von Frey细丝和热板测试评估疼痛。通过番红O/快速绿色染色、免疫荧光显微镜和RT-qPCR,综合分析膝关节、脊髓、背根神经节和远端结肠的关节病理和疼痛标志物。LA急性减轻炎性膝关节疼痛,并防止OA进一步进展。LA的治疗效果得到了我们检查的组织中软骨降解酶、疼痛标志物和炎症因子显著减少的支持。这一发现表明LA对OA可能具有临床效应。通过16 S rRNA基因扩增子测序分析评估LA处理对粪便微生物组的影响。与媒介物处理的小鼠相比,LA显著改变了粪便微生物群(PERMANOVA p < 0.009)。我们的临床前OA动物模型揭示了LA的显著OA疾病修饰作用,如通过快速关节疼痛减轻、软骨保护和生态失调逆转所反映的。我们的研究结果表明,LA治疗具有有益的全身效应,可能被开发为安全的OA疾病缓解药物(OADMD)。
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD).
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