We selected participants from the NHANES database from 2005 to 2016 for this cross-sectional analysis. Logistic regression and other analytical methods were utilized to analyze the relationship between the intake of dietary live microbes and nondietary prebiotic/probiotic and the prevalence of osteoarthritis (OA) and rheumatoid arthritis (RA). The findings demonstrated a direct relationship between the consumption of nondietary prebiotic/probiotic and the prevalence of developing OA, whereas a greater consumption of dietary live microbes is associated with a lower occurrence of RA. (Graphical abstract was created with BioRender.com).

Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus , which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen‐induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC‐MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ ‐glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production.

Rheumatoid arthritis is characterized by a burst of inflammation, the destruction of cartilage and the abundant release of inflammatory factors such as IL-1β. Thus, the effect of IL-1β on cartilage was examined in this study. IL-1β could cause lipid peroxidation and disturbances in iron metabolism by increasing the expression of NCOA4 and decreasing the expression of FTH, which also induced ferritinophagy. In addition, the expression of the key antioxidant proteins SLC7A11 and GPX4 was inhibited by IL-1β, resulting in ferroptosis in chondrocytes. Spermidine (SPD), a low-molecular-weight aliphatic nitrogen-containing compound that widely exists in animals, has been reported to be an antioxidant. In our study, we found that SPD could inhibit ferritinophagy and reverse the decrease in the expression of SLC7A11 and GPX4. Therefore, we uncovered one of the molecular mechanisms of cartilage destruction and inflammation and provide a potential polyamine for the treatment of RA.

PURPOSE:Basal metabolic rate (BMR) as one of the most basic and significant indicators of metabolism has been associated with human health. Previous studies showed that the development of rheumatoid arthritis (RA) is linked to BMR; however, the causal relationship between BMR and RA is unknown. Thus, we aimed to explore the causal relationship between BMR and RA as well as RA-related factors.METHODS:Mendelian randomization (MR) analysis was performed on collected genome-wide association studies information. The effect of horizontal pleiotropy was detected by MR-PRESSO and MR-Radial. Five MR analysis methods were applied, including inverse variance weighted, MR-Egger, weighted median, weighted mode, and simple mode. Four sensitivity analysis methods were used for the validation of the significant MR analysis results. A two-component mixture of regressions method was additionally used to validate single nucleotide polymorphisms and to verify results.RESULTS:Genetically, there is a causal effect of BMR on overall RA (odds ratio = 1.25, 95% confidence interval: 1.07-1.47, PIVW = .006), seropositive RA (odds ratio = 1.20, 95% confidence interval: 1.01-1.44, PIVW = .035), and seronegative RA (odds ratio = 1.36, 95% confidence interval: 1.04-1.78, PIVW = .023). Sensitivity analyses validated the robustness of the above associations. No evidence supported the effect of RA on BMR. Moreover, BMR showed no causal relationship with rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, interleukin-1β, tumor necrosis factor-α, and matrix metallopeptidase 3.CONCLUSION:MR results implied the causal effect of BMR on RA and raised our attention to the importance of BMR in RA's pathology.

Background: In patients with traumatic brain injury (TBI) combined with long bone fracture, the fracture healing is always faster than that of patients with single fracture, which is characterized by more callus growth at the fracture site and even ectopic ossification. Exosomes are nanoscale membrane vesicles secreted by cells, which contain cell-specific proteins, miRNAs, and mRNAs. Methods: In this study, we used exosomes as the entry point to explore the mechanism of brain trauma promoting fracture healing. We established a model of tibia fracture with TBI in mice to observe the callus growth and expression of osteogenic factors at the fracture site. Blood samples of model mice were further collected, exosomes in plasma were extracted by ultra-centrifugation method, and then identified and acted on osteoblasts cultured in vitro. The effects of exosomes on osteoblast differentiation at the cell, protein and gene levels were investigated by Western Blot and q-PCR, respectively. Furthermore, miRNA sequencing of exosomes was performed to identify a pattern of miRNAs that were present at increased or decreased levels. Results: The results suggested that plasma exosomes after TBI had the ability to promote the proliferation and differentiation of osteoblasts, which might be due to the increased expression of osteoblast-related miRNA in exosomes. They were transmitted to the osteoblasts at the fracture site, so as to achieve the role of promoting osteogenic differentiation. Conclusion: The TBI-derived exosomes may have potential applications for promoting fracture healing in future. The Translational Potential of this Article: Plasma exosomes early after TBI have the ability to promote osteoblast proliferation and differentiation. The mechanism may be achieved by miRNA in exosomes. Plasma exosomes may be used as breakthrough clinical treatment for delayed or non-union fractures.

Background Inflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive. Results Here, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles. Conclusions Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production. Graphic Abstract