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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.

MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. The role of miR‐206 and E74‐like factor 3 (Elf3) has been identified in osteoarthritis (OA), while the effect of exosomal miR‐206 from bone marrow mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to explore the role of exosomal miR‐206 from BMSCs in OA with the involvement of Elf3. BMSCs and BMSC‐derived exosomes (BMSC‐exos) were obtained and identified. OA mouse models were constructed by anterior cruciate ligament transection and then treated with BMSC‐exos or BMSC‐exos containing miR‐206 mimic/inhibitor. The expression of miR‐206, Elf3, inflammatory factors, osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The pathological changes in mouse femur tissues were observed. The mouse osteoblasts were identified and treated with untransfected or transfected BMSC‐exos, and then, the expression of miR‐206, Elf3, OCN and BMP2 was determined. The alkaline phosphatase (ALP) activity, calcium deposition level, OCN secretion, proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. MiR‐206 was down‐regulated while Elf3 was up‐regulated in OA animal and cellular models. Exosomal miR‐206 ameliorated inflammation and increased expression of OCN and BMP2 in mouse femoral tissues. Moreover, exosomal miR‐206 promoted ALP activity, calcium deposition level, OCN secretion and proliferation and inhibited apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR‐206 up‐regulation‐induced effects on OA osteoblasts. BMSC‐derived exosomal miR‐206 promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. Our research may provide novel targets for OA treatment.

IntroductionIn the present research, we formulated a modern chemotherapeutic drug by silver nanoparticles (AgNPs) containing Nigella sativa aqueous extract for the treatment of bone tumor.Material and methodsCharacterization of AgNPs was done by UV–Visible Spectroscopy (UV-Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant properties of AgNO3, N. sativa, and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-bone tumor effects of AgNO3, N. sativa, and AgNPs, MTT assay was used on the human bone Ewing’s sarcoma (CADO-ES1 and MHH-ES1), human bone osteosarcoma (HOS and MG-63), and human bone chondrosarcoma (SW-1353 and CH-3573) cell lines.ResultsDPPH test revealed similar antioxidant potentials for N. sativa, AgNPs, and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-bone tumor properties dose-dependently against CADO-ES1, MHH-ES1, HOS, MG-63, SW-1353, and CH-3573 cell lines without any cytotoxicity on the normal cell line. The best result of anti-bone tumor properties of AgNPs against the above cell lines was seen in the case of the MG-63 cell line.ConclusionsAccording to the above findings, the silver nanoparticles containing N. sativa aqueous extract can be administrated in humans for the treatment of several types of bone tumors.

Rheumatoid arthritis (RA) is a chronic and inflammatory synovitis systemic disease. Due to the unknown pathogenesis, this study was to investigate the effect of microRNA (miR)-411 on apoptosis and joint function of synoviocytes in RA mice via RIPK1-mediated NF-κB signaling pathway. The collagen-induced arthritis model mice were induced via collagen type II and Freund’s adjuvant. The mice were injected with miR-411 mimics, si-RIPK1 or miR-411 mimics + oe-RIPK1 to figure out their roles in cell apoptosis and inflammation of synovial tissues. Synoviocytes were grouped as in animal experiments. Proliferation and apoptosis of synoviocytes were detected upon treatment with overexpressed miR-411 and silenced RIPK1. The expression of miR-411, RIPK1 and NF-κB in synovial tissues and synoviocytes of RA mice was detected by RT-qPCR and Western blot analysis. Poorly expressed miR-411, and highly expressed NF-κB and RIPK1 existed in synovial tissue and synoviocytes of RA. Additionally, it was found that si-RIPK1 decreased NF-κB expression, and miR-411 mimics decreased both RIPK1 and NF-κB. MiR-411 had a targeted relationship with RIPK1. si-RIPK1 or miR-411 mimics promoted cell apoptosis and strained inflammation in synovial tissues of mice with RA. Overexpressed miR-411 or silencing RIPK1 inhibited the proliferation and promoted apoptosis of synoviocytes of RA mice. Up-regulation of miR-411 or down-regulation of RIPK1 had a certain inhibitory effect on RA. This study suggests that up-regulated miR-411 or down-regulated RIPK1 promoted apoptosis and inhibited proliferation of synoviocytes of RA mice, which may be related to the inhibition of NF-κB activation.

Background Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammatory changes. This work aims to investigate the protective role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) against the apoptosis of chondrocytes. Methods Chondrocyte cell lines, CHON-001, and ATDC5 were treated with different doses of interleukin-1β (IL-1β) to mimic the inflammatory response during OA pathogenesis. Quantitative real-time polymerase chain reaction was performed to measure MEG3, miR-9-5p, and Krüppel-like factor 4 (KLF4) mRNA expression levels. MEG3 and KLF4 overexpression plasmids, MEG3 shRNA, miR-9-5p mimics, and miR-9-5p inhibitors were transfected into the cells. Cell counting kit-8, wound healing assay, and flow cytometry were conducted to determine cell viability, migration, and apoptotic rate. Dual-luciferase reporter assay was adopted to verify the targeting relationships among MEG3, miR-9-5p, and KLF4. Western blot was used to detect KLF4 protein expression. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors. Results MEG3 expression in chondrocytes was down-regulated by the stimulation of IL-1β, and MEG3 negatively regulated miR-9-5p expression but positively regulated KLF4 expression. MEG3 overexpression strengthened the viability and migration of CHON-001 and ATDC5 cells but restrained the apoptosis and inflammatory response, while MEG3 knockdown had opposite effects. miR-9-5p inhibition or KLF4 overexpression could counteract the effects of MEG3 knockdown on chondrocytes. Besides that, MEG3 was proved to be a molecular sponge for miR-9-5p, and KLF4 was verified as the target of miR-9-5p. Conclusion MEG3 can promote chondrocyte proliferation and migration and inhibit apoptosis and inflammation by sponging miR-9-5p to induce KLF4 expression, which provides a promising therapy target for OA treatment.

An anchor bearing plate transfers the anchoring force from anchor plate to the concrete and the pre-stress is formed in the concrete structure. Currently, the main type of anchor bearing plate is cast iron. It is brittle during transportation and tension process. This paper presents a new type of anchor bearing plate combined stamping with welding forming. The structure of the new type anchor bearing plate is introduced. The stress states of the anchor bearing plate and anchorage zone under work are studied. Various specifications of anchor bearing plate are studied by ANSYS finite element analysis software following the AASHTO specification. The analysis results are compared with the results of the same type of OVM round-shaped anchor plate. The study results show that the new pre-stressed anchor plates combined stamping with welding forming are feasible and more sturdy which can meet the engineering demand.

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.