Oxidative stress plays a crucial role in the occurrence and development of osteoarthritis (OA) through the activation of endoplasmic reticulum (ER) stress. Curcumin is a polyphenolic compound with significant antioxidant and anti-inflammatory activity among various diseases. To elucidate the role of curcumin in oxidative stress-induced chondrocyte apoptosis, this study investigated the effect of curcumin on ER stress-related apoptosis and its potential mechanism in oxidative stress-induced rat chondrocytes. The results of flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed that curcumin can significantly attenuate ER stress-associated apoptosis. Curcumin inhibited the expression of cleaved caspase3, cleaved poly (ADP-ribose) polymerase (PARP), C/EBP homologous protein (CHOP), and glucose-regulated protein78 (GRP78) and upregulated the chondroprotective protein Bcl2 in TBHP-treated chondrocytes. In addition, curcumin promoted the expression of silent information regulator factor 2-related enzyme 1 (SIRT1) and suppressed the expression of activating transcription factor 4 (ATF4), the ratio of p-PERK/PERK, p-eIF2α/eIF2α. Our anterior cruciate ligament transection (ACLT) rat OA model research demonstrated that curcumin (50 mg/kg and 150 mg/kg) ameliorated the degeneration of articular cartilage and inhibited chondrocyte apoptosis in ACLT rats in a dose-dependent manner. By applying immunohistochemical analysis, we found that curcumin enhanced the expression of SIRT1 and inhibited the expression of CHOP and cleaved caspase3 in ACLT rats. Taken together, our present findings firstly indicate that curcumin could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in tert-Butyl hydroperoxide- (TBHP-) treated rat chondrocytes and ameliorated osteoarthritis development in vivo.

Background: Surgical site infection (SSI) continues to be one of the most common postoperative complications. In our previous study, surgical mask (SM) bioburden was identified to be a potential source of SSI. In the present study, we investigated the factors involved in SM bioburden.Methods: Bioburdens of the disposable SM (A: medical mask; B: medical surgical mask) and newly laundered cloth SM (C) were tested by immediately making an impression of the external surface of the mask on sterile culture media. SM microstructure was observed using a scanning electron microscope (SEM). Filtering efficiency and airflow resistance were evaluated with TSI Automated Filter Tester 8130 (TSI Incorporated) according to GB/19083-2010. Whether speaking during operation and washing the face pre-operatively affect SM bioburdens was also evaluated. Surgical procedures were performed in a dynamic operation room. Fifty cases of mask use were enrolled in this study. Results:The bioburden of mask A was the highest. The bioburden of mask B was the lowest. Mask C possessed the lowest filtering efficiency and the highest airflow resistance. SM bioburden was higher in the speaking group. SM bioburden showed no significant difference after washing the face, despite the finding that washing could significantly reduce facial bioburden.Conclusions: Multiple factors influence SM bioburdens. Mask B showed the lowest bioburden and best protection effects. Mask C is not recommended to be used, especially considering that surgeons do not wash the cloth masks daily. Unnecessary talking during operation is not recommended, and washing the face before surgery is not strictly necessary.

The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3Dprinted PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation efficacy in vivo, the rabbit radial long bone defect model was established. In the first stage, polymethylmethacrylate (PMMA) was inserted into the bone defect to stimulate the formation of IM; in the second stage, iliac crest bone graft (ICBG) with IM, PLA-HA alone with the removal of IM, PLA-HA with IM, and PLA-HA in conjunction with IM and eBM were sequentially applied to repair the long bone defect. At 8, 12, and 16 weeks, X-ray plain radiography, microcomputed tomography, and histological analysis were performed to evaluate the efficacy of bone repair and bone regeneration in each group. We found that IM combined with PLA-HA and eBM prominently enhanced bone repair and reconstruction, equivalent to that of IM/ICBG. Taken together, the data suggest that PLA-HA loaded with eBM combined with IM can be an alternative to IM with bone autografts for the treatment of large bone defects.

Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. Conclusion The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

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Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle‐mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p‐38α/β signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p‐38α/β RNA. We used enzyme‐linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro‐inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ‐CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro‐inflammatory factors were released. Titanium particle‐mediated M1 macrophage polarization, which caused the release of pro‐inflammatory factors through the p‐38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.

The present study investigated the role of bidirectional ephrin-B2/erythropoietin-producing human hepatocellular receptor 4 (ephB4) signaling in the regulation of wear particle-mediated osteoclastogenesis in vitro. Mouse bone marrow macrophages (BMMs) were induced into osteoclasts by receptor activator of nuclear factor-κB ligand (RANKL, 50 ng/ml). EphB4-Fc, an osteoblast membrane surface receptor (4 µg/ml), was used to stimulate the ephrin-B2 ligand of osteoclasts in the presence and absence of titanium (Ti). Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the number of osteoclasts, and phalloidin staining was used to examine the cytoskeletons of the osteoclasts. A bone pit absorption experiment was used to measure osteoclast function. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to examine osteoclastogenesis. ELISAs were used to detect the production of inflammatory factors. The data demonstrated that Ti significantly promoted the differentiation of BMMs into mature osteoclasts in the presence of RANKL and significantly promoted expression of the ephrin-B2, nuclear factor of activated T-cells 1 (NFATc1), TRAP, Fos proto-oncogene, AP-1 transcription factor subunit (C-FOS), and matrix metalloproteinase 9 (MMP9) genes. Phalloidin and TRAP staining revealed that following the addition of ephB4-Fc, the number, size and cytoskeletal elements of Key words: osteoclasts, osteoblasts, remodeling, ephrin-B2, osteoclastogenesis osteoclasts were significantly decreased compared with those in the titanium particle group without ephB4-Fc. Compared with the titanium particle group, the bone pit absorption experiment revealed significantly decreased absorption pit areas in the titanium particle+ephB4-Fc group. The expression of the NFATc1, TRAP, C-FOS and MMP9 genes was markedly decreased in the ephB4-Fc group; however, the expression of the ephrin-B2 gene was increased compared with the Ti particle group without ephB4-Fc after 5 days. Production of inflammatory cytokines was inhibited by Ti particles through bidirectional signals. Addition of ephB4-Fc inhibited the osteoclast-mediated formation of Ti particles via bidirectional ephrin-B2/ephB4 signaling. Activation of this bidirectional signaling pathway may be a potential clinical treatment for osteolysis surrounding prostheses.