Abstract
The human gut microbiota has been proven to have great effects on the regulation of bone health. However, the association between gut microbiota and particle-induced osteolysis, which is the primary cause of aseptic loosening, is still unknown. In this study, we used a combination of wide-spectrum antibiotics to eliminate the majority of gut microbiota and found that reduction of gut commensal bacteria significantly alleviated the progression of osteolysis, in which anaerobe was the biggest culprit in the exacerbation of osteolysis. Furthermore, colonization of enteropathogenic Escherichia coli (EPEC), a subspecies of anaerobe, could promote the development of particle-induced osteolysis by increasing the secretion of peripheral 5-hydroxytryptamine (5-HT) from the colon. Elevated 5-HT level decreased the phosphorylation of CREB and inhibited the proliferation of osteoblasts. Collectively, these results indicated EPEC colonization suppressed the bone formation and aggravated particle-induced osteolysis in vivo. Thus, clearance of EPEC is expected to become a potential preventive approach to treat debris-induced osteolysis and aseptic loosening.
Highlights
Total hip arthroplasty (THA) is considered the most effective surgery performed to treat end-stage joint diseases and severe hip trauma (Goodman et al, 2014; Cherian et al, 2015)
In order to evaluate the effect of gut microbiota on CoCrMo particles (CoPs)-induced osteolysis, we used an antibiotic cocktail (Abx), broad-spectrum antibiotics consisting of ampicillin, vancomycin, neomycin, metronidazole, and amphotericin B which were not reported to have an association with osteolysis, to eliminate intestinal microbiota
The results showed that the expression of tryptophan hydroxylase 1 (TpH1) remained unchanged while the level of serotonin transporter (SERT) was significantly downregulated after administration of enteropathogenic Escherichia coli (EPEC) compared with that of CoPs and K12 (Figures 5D, E)
Summary
Total hip arthroplasty (THA) is considered the most effective surgery performed to treat end-stage joint diseases and severe hip trauma (Goodman et al, 2014; Cherian et al, 2015). In view of the above mechanism, the current treatment measures for this complication are generally aimed at reducing bone resorption by EPEC Mediates CoP-Induced Osteolysis inhibiting osteoclasts and promoting bone formation by activating osteoblasts, including bisphosphonates, nonsteroidal anti-inflammatory drugs, and TNF inhibitors (Deng et al, 2017a). These potential approaches could not achieve the desired effect due to their poor clinical performance and various side effects. Our study found that Lacticaseibacillus casei, a common probiotic, could reduce particle-induced osteolysis by mediating macrophage polarization, indicating that the gut microbiota (GM) may be implicated in the progression of aseptic loosening (Wang et al, 2017a)
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