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Objective: Over the years, microRNAs (miRNAs) have been involved in the pathogenesis of rheumatoid arthritis (RA). We aim to investigate the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomal miR-140-3p in RA development. Methods: Exosomes(exo) were isolated from human umbilical cord-derived mesenchymal stem cells (HUCMSCs), and this isolation was followed by the transfer of miR-140-3p. RA rat models were constructed by collagen II adjuvant and respectively treated with HUCMSCs-exo or HUCMSCs-exo carrying miR-140-3p mimic/inhibitor, and expression of miR-140-3p and serum- and glucocorticoid-inducible kinase 1 (SGK1) was assessed. Then, RA score and inflammation scoring, fibrosis degree and apoptosis, serum inflammatory response and oxidative stress in joint tissues were determined. The RA synovial fibroblasts (RASFs) were extracted from rats and identified. Conducted with relative treatment, the migration, proliferation and apoptosis in RASFs were determined. Results: MiR-140-3p was decreased while SGK1 was increased in RA rats. HUCMSCs-exo or upregulated exosomal miR-140-3p improved pathological changes and suppressed inflammation, oxidative stress and fibrosis in RA rats, and also constrained and RASF growth. Overexpression of SGK1 reversed the inhibition of RASF growth caused by overexpression of miR-140-3p. Conclusion: Upregulated exosomal miR-140-3p attenuated joint injury of RA rats by silencing SGK1. This research provided further understanding of the role of exosomal miR-140-3p in RA development. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment. [Display omitted] • A trapping strategy inspired by macrophages capturing opsonized nanoparticles. • Artificial opsonized nanoparticle (IgG/Bb@BRPL) selectively targets M1 macrophage. • IgG/Bb@BRPL repolarizes M1 to M2 by ROS scavenging and NF-κB pathway deactivation. • IgG/Bb@BRPL restores metabolic function of chondrocytes in osteoarthritis condition. • Opsonization-based drug delivery strategy is promising for osteoarthritis treatment. [ABSTRACT FROM AUTHOR]

Background: The maintenance of nucleus pulposus (NP) viability in vitro is difficult. The annulus fibrosus (AF) pathway reflects one nutrient transport channel and may have an important effect on NP viability in disc organ cultures. The present study describes a feasible disc pre-treatment involving the AF and investigates its efficacy in improving NP bioactivity in an in vitro disc bioreactor culture.Methods: Rabbit discs that were randomly assigned to the experimental group (EG) were pretreated via the surgical removal and controlled trypsinization of the outer AF. The discs in the control group (CG) did not receive any special treatment. All discs were organ-cultured in a self-developed bioreactor. Solute transport into the central NP was measured using a methylene blue solution. On days 7 and 14, histological properties, cell viability, cell membrane damage, gene expression and matrix composition within the NP in these two groups were compared with each other and with the corresponding parameters of fresh NP samples. Additionally, the structures of the outer AF and the cartilage endplate (CEP) following pre-treatment were also assessed.Results: The outer AF in the EG became disorganized, but no specific changes occurred in the CEP or the inner AF following pre-treatment. The discs in the EG exhibited increased penetration of methylene blue into the central NP. On days 7 and 14, the NP bioactivity in the EG was improved compared with that of the CG in terms of cell viability, cell membrane damage, gene expression profile and matrix synthesis. Moreover, cell viability and matrix synthesis parameters in the EG were more similar to those of fresh samples than they were to the same parameters in the CG on day 14.Conclusions: Using this disc pre-treatment, i.e., the surgical removal and controlled trypsinization of the outer AF, NP bioactivity was better maintained for up to 14 days in an in vitro disc bioreactor culture. [ABSTRACT FROM AUTHOR]