Background Recent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism. Methods Highly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro. The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis. Results Bioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased. Conclusions BMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR.

Hyperuricemia is a metabolic disorder that is essential to the development of inflammatory gout, with increasing prevalence over recent years. Emerging clinical findings has evidenced remarkable tendon damage in individuals with longstanding asymptomatic hyperuricemia, yet the impact of hyperuricemia on tendon homeostasis and associated repercussions is largely unknown. Here, we investigated whether asymptomatic hyperuricemia was associated with spontaneous ruptures in the Achilles tendon and the pathological effect of hyperuricemia on the tendon stem/progenitor cells (TSPCs). Significantly higher serum uric acid (SUA) levels were found in 648 closed Achilles tendon rupture (ATR) patients comparing to those in 12559 healthy volunteers. In vitro study demonstrated that uric acid (UA) dose dependently reduced rat Achilles TSPC viability, decreased the expressions of tendon collagens, and deformed their structural organization while significantly increased the transcript levels of matrix degradative enzymes and proinflammatory factors. Consistently, marked disruptions in Achilles tendon tissue structural and functional integrity were found in a rat model of hyperuricemia, together with enhanced immune cell infiltration. Transcriptome analysis revealed a significant elevation in genes involved in metabolic stress and tissue degeneration in TSPCs challenged by hyperuricemia. Specifically, reduced activity of the AKT-mTOR pathway with enhanced autophagic signaling was confirmed. Our findings indicate that asymptomatic hyperuricemia may be a predisposition of ATR by impeding the normal functions of TSPCs. This information may provide theoretical and experimental basis for exploring the early prevention and care of ATR.

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Background. Pigmented villous nodular synovitis (PVNS) is a tumor-like proliferative disease characterized by impairment of daily activities, decreased quality of life, and a high recurrence rate. However, the specific pathological mechanisms are still ill-defined and controversial. The purpose of this study was to define potential diagnostic markers and evaluate immune cell infiltration in the pathogenesis of PVNS. Method. The expression profile of GSE3698 was reanalyzed in the Gene Expression Omnibus (GEO) database. First, differentially expressed genes (DEGs) were identified using the R package “limma” and analyzed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Next, the DEGs were imported into the STRING database and Cytoscape to construct a protein–protein interaction (PPI) network. Then, cytoHubba and ROC curve analyses were used to determine potential diagnostic biomarkers of PVNS. Finally, we used CIBERSORT to estimate the proportions of 22 immune cell subtypes in PVNS and analyzed the correlation between diagnostic markers and infiltrating immune cells. Result. We found 139 DEGs (including 93 upregulated genes and 46 downregulated genes). TYROBP, FCER1G, LAPTM5, and HLA-DPB1 were identified as potential diagnostic biomarkers of PVNS. Immune cell infiltration analysis indicated that neutrophils and M2 macrophages might be associated with the genesis and progression of PVNS. Furthermore, our correlation analysis of diagnostic markers and infiltrating immune cells found that TYROBP, FCER1G, LAPTM5, and HLA-DPB1 were positively correlated with M2 macrophage infiltration and that neutrophils, TYROBP, FCER1G, and LAPTM5 were negatively correlated with plasma cell infiltration. Conclusions. We identified TYROBP, FCER1G, LAPTM5, and HLA-DPB1 as potential diagnostic markers for PVNS and concluded that immune cell infiltration plays an important role in the genesis and progression of PVNS.