Correlation between Mitochondria-Associated Endoplasmic Reticulum Membrane-Related Genes and Cellular Senescence-Related Genes in Osteoarthritis.

BACKGROUND: The role of mitochondria-associated endoplasmic reticulum membrane (MAM) formation in the development of osteoarthritis (OA) is yet unclear. METHODS: A mix of bioinformatics methods and in vitro experimental methodologies was used to study and corroborate the role of MAM-related genes and cellular senescence-related genes in the development of OA. The Gene Expression Omnibus database was used to obtain the microarray information that is relevant to the OA. Several bioinformatic methods were employed to carry out function enrichment analysis and protein-protein correlation analysis, build the correlation regulatory network, and investigate potential relationships between MAM-related genes and cellular senescence-related genes in OA. These methods also served to identify the MAM-related and OA-related genes (MAM-OARGs). RESULTS: For the additional functional enrichment analysis, a total of 13 MAM-OARGs were detected. The correlation regulatory network was also created. Hub MAM-OARGs were shown to have a strong correlation with genes relevant to cellular senescence in OA. Results of in vitro experiments further demonstrated a positive correlation between MAM-OARGs (PTPN1 and ITPR1) and cellular senescence-related and OA-related genes. CONCLUSIONS: As a result, our findings can offer new insights into the investigations of MAM-related genes and cellular senescence-related genes, which could be linked to the OA as well as brand-new potential treatment targets.

TiO2 nanotube topography enhances osteogenesis through filamentous actin and XB130-protein-mediated mechanotransduction.

TiO2 nanotube topography, as nanomechanical stimulation, can significantly promote osteogenesis and improve the osteointegration on the interface of implants and bone tissue. However, the underlying mechanism has not been fully elucidated. XB130 is a member of the actin filament-associated protein family and is involved in the regulation of cytoskeleton and tyrosine kinase-mediated signalling as an adaptor protein. Whether XB130 is involved in TiO2 nanotubes-induced osteogenic differentiation and how it functions in mechano-biochemical signalling transduction remain to be elucidated. In this study, the role of XB130 on TiO2 nanotube-induced osteogenesis and mechanotransduction was systematically investigated. TiO2 nanotube topography was fabricated via anodic oxidation and characterized. The osteogenic effect was significantly accelerated by the TiO2 nanotube surface in vitro and vivo. XB130 was significantly upregulated during this process. Moreover, XB130 overexpression significantly promoted osteogenic differentiation, whereas its knockdown inhibited it. Filamentous actin depolymerization could change the expression and distribution of XB130, thus affecting osteogenic differentiation. Mechanistically, XB130 could interact with Src and result in the activation of the downstream PI3K/Akt/GSK-3ß/ß-catenin pathway, which accounts for the regulation of osteogenesis. This study for the first time showed that the enhanced osteogenic effect of TiO2 nanotubes could be partly due to the filamentous actin and XB130 mediated mechano-biochemical signalling transduction, which might provide a reference for guiding the design and modification of prostheses to promote bone regeneration and osseointegration. STATEMENT OF SIGNIFICANCE: TiO2 nanotubes topography can regulate cytoskeletal rearrangement and thus promote osteogenic differentiation of BMSCs. However, how filamentous actin converts mechanical stimulus into biochemical activity remains unclear. XB130 is a member of actin filament-associated protein family and involves in the regulation of tyrosine kinase-mediated signalling. Therefore, we hypothesised that XB130 might bridge the mechano-biochemical signalling transduction during TiO2 nanotubes-induced osteogenic differentiation. For the first time, this study shows that TiO2 nanotubes enhance osteogenesis through filamentous actin and XB130 mediated mechanotransduction, which provides new theoretical basis for guiding the design and modification of prostheses to promote bone regeneration and osseointegration.

Active Micro-Nano-Collaborative Bioelectronic Device for Advanced Electrophysiological Recording.

The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience. In recent years, active micro/nano-bioelectronic devices have undergone significant advancements, thereby facilitating the study of electrophysiology. The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale. In this paper, we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electro-excitable cells, focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals. Looking forward to the possibilities, challenges, and wide prospects of active micro-nano-devices, we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.

Biomimetic Injectable Hydrogel Based on Methacrylate-Modified Silk Fibroin Embedded with Kartogenin for Superficial Cartilage Regeneration.

The weak regeneration ability of chondrocytes is one of the main reasons that limit the therapeutic effect of clinical cartilage injury. Injectable hydrogels are potential scaffolds for cartilage tissue engineering with advantages such as minimally invasive surgery, porous structure, and drug sustained-release ability. At present, many biomaterials have been developed for the repair of deep cartilage defects. However, cartilage injury often begins on the surface, which requires us to propose a treatment strategy suitable for superficial cartilage injury repair. In this study, we fabricated a biomimetic injectable hydrogel based on methacrylate-modified silk fibroin (SilMA) embedded with kartogenin (KGN). The SilMA/KGN hydrogels have good biohistocompatibility and the ability to promote cartilage differentiation. In addition, SEM results show that it has a porous structure conducive to cell adhesion and proliferation. Most importantly, it has demonstrated remarkable superficial cartilage repair ability in vivo, showing potential in cartilage tissue engineering.

The efficacy and safety of low-molecular-weight heparin in patients undergoing knee arthroscopic surgery and anterior cruciate ligament reconstruction.

Purpose: To inveatigate how effective LMWH was at preventing venous thromboembolism (VTE), major bleeding events, and minor bleeding events after simple knee arthroscopic surgery and anterior cruciate ligament reconstruction (ACLR). Methods: We conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, and the CNKI database for potentially eligible articles. The outcomes were evaluated in terms of odds ratio (OR) and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the Stata software and subgroup analyses were performed based on the surgical setting including ACLR and simple knee arthroscopic surgery. Results: A total of eight studies with 2249 patients and 1794 controls were included in this meta-analysis. In patients undergoing simple knee arthroscopic surgery, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic deep venous thrombosis (DVT), symptomatic pulmonary embolism (PE), symptomatic VTE, and did not increase the risk of major bleeding events, but did have a higher risk of minor bleeding events (OR = 1.95, 95% CI 1.34-2.84, P = 0.000) and a lower risk of asymptomatic DVT (OR = 0.14, 95% CI 0.04-0.53, P = 0.004) in comparison with non-LMWH prophylaxis. In patients undergoing ACLR, LMWH prophylaxis did not bring a significant reduction in the risk of symptomatic DVT, symptomatic PE, symptomatic VTE, and did not increase the risk of major bleeding events and minor bleeding events, but did have a lower risk of asymptomatic DVT (OR = 0.43, 95% CI 0.23-0.78, P = 0.006). Conclusion: When compared to a control group, this meta-analysis found that LMWH had little potential benefit in preventing major VTE (symptomatic VTE, symptomatic DVT, and symptomatic PE) after simple knee arthroscopy and ACLR. As a result, LMWH should not be considered routinely in patients undergoing knee arthroscopic surgery.

Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration.

With the increasing incidence of knee osteoarthritis (KOA), the reparation of cartilage defects is gaining more attention. Given that tissue integration plays a critical role in repairing cartilage defects, tissue adhesive hydrogels are highly needed in clinics. We constructed a biomacromolecule-based bioadhesive matrix hydrogel and applied it to promote cartilage regeneration. The hydrogel was composed of methacrylate gelatin and N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitroso) butyl amide modified hyaluronic acid (HANB). The methacrylate gelatin provided a stable hydrogel network as a scaffold, and the HANB served as a tissue-adhesive agent and could be favorable for the chondrogenesis of stem cells. Additionally, the chemically modified HA increased the swelling ratio and compressive modulus of the hydrogels. The results of our in vitro study revealed that the hydrogel was compatible with bone marrow stromal cells. In vivo, the hyaluronic-acid-containing hydrogels were found to promote articular cartilage regeneration in the defect site. Therefore, this biomaterial provides promising potential for cartilage repair.

Chondroitin Sulfate Improves Mechanical Properties of Gelatin Hydrogel for Cartilage Regeneration in Rats.

Cartilage injury is a common disease in daily life. Especially in aging populations, the incidence of osteoarthritis is increasing. However, due to the poor regeneration ability of cartilage, most cartilage injuries cannot be effectively repaired. Even cartilage tissue engineering still faces many problems such as complex composition and poor integration of scaffolds and host tissues. In this study, chondroitin sulfate, one of the main components of extracellular matrix (ECM), is chosen as the main natural component of the material, which can protect cartilage in a variety of ways. Moreover, the results show that the addition of chondroitin sulfate improves the mechanical properties of gelatin methacrylate (GelMA) hydrogel, making it able to effectively bear mechanical loads in vivo. Further, chondroitin sulfate is modified to obtain the oxidized chondroitin sulfate (OCS) containing aldehyde groups via sodium periodate. This special group improves the interface integration and adhesion ability of the hydrogel to host cartilage tissue through schiff base reactions. In summary, GelMA/OCS hydrogel is a promising candidate for cartilage regeneration with good biocompatibility, mechanical properties, tissue integration ability, and excellent cartilage repair ability.

Mechanisms of ferroptosis with immune infiltration and inflammatory response in rotator cuff injury.

The processes driving ferroptosis and rotator cuff (RC) inflammation are yet unknown. The mechanism of ferroptosis and inflammation involved in the development of RC tears was investigated. The Gene Expression Omnibus database was used to obtain the microarray data relevant to the RC tears for further investigation. In this study, we created an RC tears rat model for in vivo experimental validation. For the additional function enrichment analysis, 10 hub ferroptosis-related genes were chosen to construct the correlation regulation network. In RC tears, it was discovered that genes related to hub ferroptosis and hub inflammatory response were strongly correlated. The outcomes of in vivo tests showed that RC tears were related to Cd68-Cxcl13, Acsl4-Sat1, Acsl3-Eno3, Acsl3-Ccr7, and Ccr7-Eno3 pairings in regulating ferroptosis and inflammatory response. Thus, our results show an association between ferroptosis and inflammation, providing a new avenue to explore the clinical treatment of RC tears.

Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis.

BACKGROUND: Aspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo. METHODS: The effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo. RESULTS: Aspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo. CONCLUSION: Aspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

Mesenchymal Stem Cells-Hydrogel Microspheres System for Bone Regeneration in Calvarial Defects.

The repair of large bone defects in clinic is a challenge and urgently needs to be solved. Tissue engineering is a promising therapeutic strategy for bone defect repair. In this study, hydrogel microspheres (HMs) were fabricated to act as carriers for bone marrow mesenchymal stem cells (BMSCs) to adhere and proliferate. The HMs were produced by a microfluidic system based on light-induced gelatin of gelatin methacrylate (GelMA). The HMs were demonstrated to be biocompatible and non-cytotoxic to stem cells. More importantly, the HMs promoted the osteogenic differentiation of stem cells. In vivo, the ability of bone regeneration was studied by way of implanting a BMSC/HM system in the cranial defect of rats for 8 weeks. The results confirmed that the BMSC/HM system can induce superior bone regeneration compared with both the HMs alone group and the untreated control group. This study provides a simple and effective research idea for bone defect repair, and the subsequent optimization study of HMs will provide a carrier material with application prospects for tissue engineering in the future.

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/ß-Catenin.

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/ß-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/ß-catenin.

'Skywalker' surgical robot for total knee arthroplasty: An experimental sawbone study.

BACKGROUND: Currently, robot-assisted surgical systems are used to reduce the error range of total knee arthroplasty (TKA) osteotomy and component positioning. METHODS: We used 20 sawbone models of the femur and 20 sawbone models of the tibia and fibula to evaluate the osteotomy effect of 'Skywalker' robot-assisted TKA. RESULTS: The maximal movement of the cutting jig was less than 0.25 mm at each osteotomy plane. The mean and standard deviation values of the angle deviation between the planned osteotomy plane and the actual osteotomy plane at each osteotomy plane were not more than 1.03° and 0.55°, respectively. The mean and standard deviation values of absolute error of resection thickness at each osteotomy position were less than 0.78 and 0.71 mm, respectively. CONCLUSIONS: The 'Skywalker' system has good osteotomy accuracy, can achieve the planned osteotomy well and is expected to assist surgeons in performing accurate TKA in clinical applications in future.

TiO2 nanotubes regulate histone acetylation through F-actin to induce the osteogenic differentiation of BMSCs.

Bone integration on the surface of titanium prosthesis is critical to the success of implant surgery. Good Bone integration at the contact interface is the basis of long-term stability. TiO2 nanotubes have become one of the most commonly used modification techniques for artificial joint prostheses and bone defect implants due to their good biocompatibility, mechanical properties and chemical stability. TiO2 nanotubes can promote F-actin polymerization in bone mesenchymal stem cells (BMSCs) and osteogenic differentiation. The possibility of F-actin as an upstream part to regulate GCN5 initiation of osteogenesis was discussed. The results of gene loss and functional acquisition assay, immunoblotting assay and fluorescence staining assay showed that TiO2 nanotubes could promote the differentiation of BMSCs into osteoblasts. The intervention of TiO2 nanotubes can make BMSCs form stronger F-actin fibre bundles, which can drive the differentiation process of osteogenesis. Our results showed that F-actin mediated nanotube-induced cell differentiation through promoting the expression of GCN5 and enhancing the function of GCN5 and GCN5 was a key regulator of the osteogenic differentiation of BMSCs induced by TiO2 nanotubes as a downstream mediated osteogenesis of F-actin, providing a novel insight into the study of osteogenic differentiation on surface of TiO2 nanotubes.

F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through MKL1 and YAP/TAZ.

Titanium and titanium alloys are widely used in orthopedic implants. Modifying the nanotopography provides a new strategy to improve osseointegration of titanium substrates. Filamentous actin (F-actin) polymerization, as a mechanical loading structure, is generally considered to be involved in cell migration, endocytosis, cell division, and cell shape maintenance. Whether F-actin is involved and how it functions in nanotube-induced osteogenic differentiation of mesenchymal stem cells (MSCs) remain to be elucidated. In this study, we fabricated TiO2 nanotubes on the surface of a titanium substrate by anodic oxidation and characterized their features by scanning electron microscopy (SEM), X-ray energy dispersive analysis (EDS), and atomic force microscopy (AFM). Alkaline phosphatase (ALP) staining, Western blotting, qRT-PCR, and immunofluorescence staining were performed to explore the osteogenic potential, the level of F-actin, and the expression of MKL1 and YAP/TAZ. Our results showed that the inner diameter and roughness of TiO2 nanotubes increased with the increase of the anodic oxidation voltage from 30 to 70 V, while their height was 2 µm consistently. Further, the larger the tube diameter, the stronger the ability of TiO2 nanotubes to promote osteogenic differentiation of MSCs. Inhibiting F-actin polymerization by Cyto D inhibited osteogenic differentiation of MSCs as well as the expression of proteins contained in focal adhesion complexes such as vinculin (VCL) and focal adhesion kinase (FAK). In contrast, after Jasp treatment, polymerization of F-actin enhanced the expression of RhoA and transcription factors YAP/TAZ. Based on these data, we concluded that TiO2 nanotubes facilitated the osteogenic differentiation of MSCs, and this ability was enhanced with the increasing diameter of the nanotubes within a certain range (30-70 V). F-actin mediated this process through MKL1 and YAP/TAZ.

Interannual variation, ecological risk and human health risk of heavy metals in oyster-cultured sediments in the Maowei Estuary, China, from 2011 to 2018.

Heavy metals (HMs) in aquaculture-influenced sediments pose a threat to both aquatic ecosystems and human health via aquatic product intake. Based on a long-term (from 2011 to 2018) study, the concentrations of five HMs in oyster-cultured sediments in the Maowei Estuary, China, were ranked as follows: Pb (17.58 ± 10.82 mg/kg) > Cu (17.15 ± 8.61 mg/kg) > As (10.27 ± 5.24 mg/kg) > Cd (0.16 ± 0.14 mg/kg) > Hg (0.067 ± 0.033 mg/kg). These concentrations were all close to the guide values in China and those reported in other studies. However, through the Mann-Kendall test, Cu showed obvious increasing interannual trends, and according to ecological risk assessment, the sediments were highly contaminated with Cu and Hg. The health risks to local residents via oyster intake showed that both noncarcinogenic and carcinogenic risk did not exceed the safety criteria (THQ = 1, TCR = 10-6). The current study suggests that ecological and human health risks be integrated to control HMs in the Maowei Estuary.

Mechanical strain promotes osteogenic differentiation of mesenchymal stem cells on TiO2 nanotubes substrate.

Previous studies demonstrated cycle mechanical strain induced osteogenic differentiation of MSCs. But in general, MSCs are typically seeded on a flexible membrane or within a soft matrix. TiO2 nanotubes substrate topography plays a critical role in promoting the MSCs response and affects MSCs fate. Titanium implants surface modified by TiO2 nanotubes topography provides the opportunity to improve osseointegration by additionally regulating the MSCs fate. Titanium is one of most commonly used materials in the orthopedics and can undergo elastic deformation under certain mechanical stress. Therefore, for clinic trails, it is necessary to investigate the effect of mechanical strain on osteogenesis of MSCs on TiO2 nanotubes modified titanium substrate. But until now, there has been no research focused on the relationship between mechanical strain and osteogenesis of MSCs on the TiO2 nanotubes topography substrate. Here, we firstly applied the mechanical stress to the TiO2 nanotubes modified titanium specimen to investigate the effects of mechanical strain on the biological behaviors of MSCs. Our present study showed that mechanical strain promoted cell proliferation, spreading and increased vinculin expression of MSCs on the TiO2 nanotubes substrate. Additionally, mechanical strain enhanced the ALP activity and osteogenesis genes expression such as Runx2, BSP, ALP, OPN and OCN. Our results preliminarily demonstrated that mechanical strain enhanced the osteogenic differentiation of MSCs through the FAK-Erk1/2-Runx2 pathway on the TiO2 nanotubes substrate.