Clinical Research Unit, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Key Laboratory of Intelligent Critical Care and Life Support Research of Zhejiang Province, Wenzhou, 325000, China.
Probiotics Antimicrob Proteins. 2024 Apr;16(2):383-393. doi: 10.1007/s12602-023-10057-7. Epub 2023 Mar 10.
Wear particles generated from total joint replacements induce chronic osteolysis mediated by inflammatory upregulation, which leads to implant failure. Recent studies have suggested an important role of the gut microbiota in modulating the host's metabolism and immune system, leading to alterations in bone mass. Following gavage with P. histicola, micro-CT and HE staining revealed that osteolysis was significantly reduced in titanium (Ti)-treated mice. Immunofluorescence analysis revealed an increased macrophage (M)1/M2 ratio in the guts of Ti-treated mice, which decreased when P. histicola was added. P. histicola was also found to upregulate the tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the gut, reduce the levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α, primarily in the ileum and colon, and decrease the expression of IL-1β and TNF-α and increase the level of IL-10 in the serum and cranium. Furthermore, P. histicola treatment resulted in a significant downregulation of CTX-1, RANKL, and RANKL/OPG. These findings demonstrate that P. histicola significantly mitigates osteolysis in Ti-treated mice by improving intestinal microbiota that repairs intestinal leakage and reduces systemic and local inflammation which in turn inhibits RANKL expression for bone resorption. P. histicola treatment may thus be therapeutically beneficial for particle-induced osteolysis.
关节置换术后产生的磨损颗粒会引发慢性骨溶解，这种骨溶解是由炎症上调引起的，会导致植入物失效。最近的研究表明，肠道微生物群在调节宿主代谢和免疫系统方面起着重要作用，导致骨量发生变化。用 P. histicola 灌胃后，micro-CT 和 HE 染色显示钛（Ti）处理的小鼠的骨溶解明显减少。免疫荧光分析显示，Ti 处理的小鼠肠道中的巨噬细胞（M）1/M2 比值增加，当添加 P. histicola 时，该比值降低。还发现 P. histicola 上调了肠道中的紧密连接蛋白 ZO-1、occludin、claudin-1 和 MUC2，降低了肠道和结肠中白细胞介素-1β、白细胞介素-6、白细胞介素-8 和肿瘤坏死因子-α的水平，并降低了血清和颅中的白细胞介素-1β和肿瘤坏死因子-α的表达，增加了白细胞介素-10 的水平。此外，P. histicola 治疗还导致 CTX-1、RANKL 和 RANKL/OPG 的表达显著下调。这些发现表明，P. histicola 通过改善修复肠道渗漏的肠道微生物群，减少全身和局部炎症，从而抑制 RANKL 表达以促进骨吸收，从而显著减轻 Ti 处理小鼠的骨溶解。因此，P. histicola 治疗可能对颗粒诱导的骨溶解具有治疗益处。
