Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs.

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.

Fabrication and evaluation of a molecular-imprinted-polymer functionalized electrode for selective electric field-assisted solid-phase microextraction of phytohormones.

Specific extraction and separation plays a pivotal role in the accurate quantification of trace phytohormones (PHs). However, due to their high polarity, specific capture of PHs is challenging. In this study, under the assistance of electric field, a molecular-imprinted-polymer functionalized electrode (MIP@ED) was in-situ prepared using 3-indoleacetic acid (IAA) as template and employed as the adsorbent of electric field-assisted solid-phase microextraction (EA-SPME) for specific capture of PHs. Results showed that the implementation of electric field during the preparation of MIP@ED and EA-SPME procedures improved the extraction selectivity, the selective factors towards IAA and its structural analogues increased from 2.09 to 2.45 to 2.88-3.51. Under the optimum conditions, the proposed MIP@ED/EA-SPME was combined with HPLC technique to monitor trace PHs in water and agricultural products. The achieved limits of detection were in the ranges of 0.0053-0.011 µg/L and 0.048-0.12 µg/kg for water and agricultural product, respectively. The established approach was successfully applied to quantify trace PHs in real samples, and the spiked recoveries varied from 84.0 % to 118 % with good repeatability (RSDs blow 10 %). The obtained results provided clear evidence that the developed approach employing the MIP@ED/EA-SPME technique demonstrated high sensitivity, good selectivity, satisfactory reproducibility and environmental friendliness in the quantification of trace PHs in complex samples. In addition, the current study supplied a new strategy to enhance the specific recognition performance of MIP-based SPME.

E7 Peptide Enables BMSC Adhesion and Promotes Chondrogenic Differentiation of BMSCs Via the LncRNA H19/miR675 Axis.

Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.

Autophagy in the pathogenesis and therapeutic potential of post-traumatic osteoarthritis.

Autophagy, as a fundamental mechanism for cellular homeostasis, is generally involved in the occurrence and progression of various diseases. Osteoarthritis (OA) is the most common musculoskeletal disease that often leads to pain, disability and economic loss in patients. Post-traumatic OA (PTOA) is a subtype of OA, accounting for >12% of the overall burden of OA. PTOA is often caused by joint injuries including anterior cruciate ligament rupture, meniscus tear and intra-articular fracture. Although a variety of methods have been developed to treat acute joint injury, the current measures have limited success in effectively reducing the incidence and delaying the progression of PTOA. Therefore, the pathogenesis and intervention strategy of PTOA need further study. In the past decade, the roles and mechanisms of autophagy in PTOA have aroused great interest in the field. It was revealed that autophagy could maintain the homeostasis of chondrocytes, reduce joint inflammatory level, prevent chondrocyte death and matrix degradation, which accordingly improved joint symptoms and delayed the progression of PTOA. Moreover, many strategies that target PTOA have been revealed to promote autophagy. In this review,  we summarize the roles and mechanisms of autophagy in PTOA and the current strategies for PTOA treatment that depend on autophagy regulation, which may be beneficial for PTOA patients in the future.

Correlation between the Signal Intensity Alteration of Infrapatellar Fat Pad and Knee Osteoarthritis: A Retrospective, Cross-Sectional Study.

Infrapatellar fat pad (IPFP) inflammation is a common pathological manifestation in knee osteoarthritis (OA). However, the significance of IPFP signal intensity alteration for clinical diagnosis and treatment of knee OA needs further research. We assessed IPFP signal intensity alteration (0-3), IPFP maximum cross-sectional area (CSA) and IPFP depth, meniscus injury, bone marrow edema, and cartilage injury from magnetic-resonance imaging (MRI) in 41 non-KOA patients (K-L grade 0 and grade I) and 68 KOA patients (K-L grade 2,3 and 4). We found that IPFP signaling was altered in all patients with KOA whose alteration was closely related to the K-L grading. We found that the IPFP signal intensity was increased in most OA patients, especially the ones in the late stage. There were significant differences in IPFP maximum CSA and IPFP depth between groups in KOA and non-KOA patients. Moreover, Spearman correlation analysis showed that IPFP signal intensity was moderately positively correlated with age, meniscal injury, cartilage injury, and bone marrow edema, and negatively correlated with height, while not correlated with visual analogue scale (VAS) scoring and body mass index (BMI). In addition, women have higher IPFP inflammation scores on MRI than men. In conclusion, IPFP signal intensity alteration is associated with joint damage in knee OA, which may have clinical significance for diagnosing and treating KOA.

Molecularly imprinted monolith-based portable in-tip microextraction device for field specific extraction of triazine herbicides in aqueous samples followed by chromatographic quantification.

Field selective extraction is crucial for accurate monitoring of triazine herbicides (TAHs) in aqueous samples. For this purpose, using atrazine as template and 3-acrylamido phenylboronic acid as functional monomer which was quickly screened with calculation simulation technology, a new molecularly imprinted monolith-based adsorbent (MBA) was fabricated and utilized as the extraction phase of laboratory-made multichannel in-tip microextraction device (MIMD). A series of techniques were adopted to characterize the physical and chemical properties of the synthesized MBA. Under the optimized preparation conditions, the recognition factor and capture capacity of MBA towards atrazine were as high as 2.9 and 23.4 mg/g, respectively, and the enrichment factors towards TAHs located in the range of 276-359. The study about adsorption isotherm evidenced the adsorption of MBA towards atrazine was fit for Freundlich adsorption model. Under the beneficial extraction parameters, the introduced MBA/MIMD was utilized to on-site extract TAHs in a variety of aqueous samples prior to HPLC determination. High sensitivity (limit of detection: 0.25-0.64 ng/L), good precision (relative standard deviation: 1.4-9.5%) and satisfying recovery (81.0-113%) were achieved. Accuracy and reliability of the introduced method were inspected through confirmation experiments. Owing to the good results and outstanding merits, the established MBA/MIMD technique is appropriate for field sample preparation of TAHs and the developed method can be utilized to monitor TAHs residuals in various aqueous samples.

Electric field-reinforced solid phase microextraction based on anion-exchange monolith for efficient entrapment of anions in aqueous and wine samples.

In the present work, a new strategy based on electric field-reinforced solid phase microextraction (ER-SPME) for the analysis of trace inorganic anions in aqueous and wine samples was proposed. In this connection, anion-exchange monolith (AEM) was in-situ synthesized on the surface of stainless steel wire and employed as the adsorbent of ER-SPME. Variable electric fields were applied during the adsorption and desorption durations to improve the entrapment performance towards studied anions. Results revealed that the application of electric fields not only accelerated the extraction process, but also enhanced the extraction efficiencies (increased by 59-121% compared with without exertion of electric field). Under the selected extraction parameters, sensitive method with wide linear ranges (5.0-500 µg/L for BrO3- and 0.10-500 µg/L for other anions), low limits of detection (0.030-2.5 µg/L) and satisfactory precision (RSDs below 10%) was established by the combination of AEM/ER-SPME with ion chromatography with conductivity detector. The developed approach was successful used to quantify trace investigated anions in various aqueous and wine samples, and the fortified recoveries varied from 83.2 to 115%. At the same time, related adsorption and desorption mechanism under the electric field was inspected.

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression.

Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin ß1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin ß1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin ß1/ERK/VCL pathway. Our findings may provide new insights in MSCs intra-articular injection for OA treatment.

Preoperative Predictors of Prolonged Hospital Stay in Accelerated Rehabilitation for Patients Undergoing Orthopedic Surgery.

In this study, we performed a retrospective and prospective study of preoperative predictors of the length of stay (LOS) in three groups of surgical patients and conducted a clinical retrospective study of the current research status of preoperative predictors of LOS prolongation in three groups of patients under ERAS (enhanced recovery after surgery) mode, such as patient characteristics and comorbidities. Information such as patients' exercise preferences, exercise time, frequency and duration, footwear, location of knee osteoarthritis, whether there is a past history of knee injury, and smoking and drinking history was collected, and the research data of 312 patients undergoing the three operations were analyzed by SPSS. Meniscal injury-knee arthroscopy sample included a total of 104 people. Surgical sample for anterior cruciate ligament reconstruction included a total of 100 subjects. Knee osteoarthritis-knee replacement surgery sample included 148 people who were divided into two groups in a ratio of 1 : 1: one group used Mailuo Shutong pills during hospitalization (intervention group) and the other group did not (control group). The research conclusions are as follows. Meniscal Knee Arthroscopy. (1) Samples from different causes of injury showed significant differences for all injured sites. (2) Samples with different smoking and drinking histories all showed significant differences for the causes of injury. (3) Exercise hobby, exercise frequency, duration of each exercise and duration of exercise, and warm-up time before exercise all showed positive correlation. Anterior Cruciate Ligament Reconstruction Surgery. (4) Samples from different causes of injury showed significant differences for all the injured sites. (5) Age has a significant negative influence on the wearing of shoes at ordinary times. (6) Exercise hobby: the warm-up time before exercise had a significant negative influence on the injured area. (7) Two groups of analysis items of exercise frequency, exercise duration and exercise duration, preexercise warm-up time, and exercise hobby were typically positively correlated. Total Knee Arthroplasty. (8) There was a significant difference of 0.01 between the hospitalization days of the intervention group and the control group (p < 0.01), and the hospitalization days of the intervention group were significantly lower than those of the control group. These results indicated that Mailuo Shutong pills were of great significance for the treatment of orthopedic patients during the operation period in that it could effectively shorten the hospital stay of all orthopedic patients and strengthen the accelerated rehabilitation. (9) There was a significant positive correlation between the history of knee joint surgery and the use time of Mailuo Shutong pills. (10) There was a markable positive correlation between occupation and sports hobbies, sports time, frequency and duration, and footwear. There was a significant negative correlation between occupation and preexercise warm-up. (11) Exercise time, frequency, and duration have significant positive influence on BMI.

Deep Learning-Based Image Feature with Arthroscopy-Aided Early Diagnosis and Treatment of Meniscus Injury of Knee Joint.

The aim of this study is to explore the clinical effect of deep learning-based MRI-assisted arthroscopy in the early treatment of knee meniscus sports injury. Based on convolutional neural network algorithm, Adam algorithm was introduced to optimize it, and the magnetic resonance imaging (MRI) image super-resolution reconstruction model (SRCNN) was established. Peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) were compared between SRCNN and other algorithms. Sixty patients with meniscus injury of knee joint were studied. Arthroscopic surgery was performed according to the patients' actual type of injury, and knee scores were evaluated for all patients. Then, postoperative scores and MRI results were analyzed. The results showed that the PSNR and SSIM values of the SRCNN algorithm were (42.19 ± 4.37) dB and 0.9951, respectively, which were significantly higher than those of other algorithms (P < 0.05). Among patients with meniscus injury, 17 cases (28.33%) were treated with meniscus suture, 39 cases (65.00%) underwent secondary resection, 3 cases (5.00%) underwent partial resection, and 1 case (1.67%) underwent full resection. After meniscus suture, secondary resection, partial resection, and total resection, the knee function scores of patients after treatment were (83.17 ± 8.63), (80.06 ± 7.96), (84.34 ± 7.74), and (85.52 ± 5.97), respectively. There was no great difference in knee function scores after different methods of treatment (P > 0.05), and there were considerable differences compared with those before treatment (P < 0.01). Compared with the results of arthroscopy, there was no significant difference in the grading of meniscus injury by MRI (P > 0.05). To sum up, the SRCNN algorithm based on the deep convolutional network algorithm improved the MRI image quality and the diagnosis of knee meniscus injuries. Arthroscopic knee surgery had good results and had great clinical application and promotion value.

Monolith/aminated graphene oxide composite-based electric field-assisted solid phase microextraction for efficient capture of phenoxycarboxylic acids herbicides in environmental waters.

Efficient capture of strongly polar, ionizable and trace phenoxycarboxylic acids herbicides (PCAHs) from aqueous samples is essential and challenging for environmental monitoring. In the present work, electric field-assisted solid-phase microextraction (EFA-SPME) based on monolith/aminated graphene oxide composite was developed for the first time to efficiently extract trace PCAHs prior to HPLC-tandem mass spectrometry (HPLC-MS/MS) quantification. First, poly (1-allyl-3-methylimidazole difluoromethanesulfonylamide salt-co-divinylbenzene/ethylene dimethacrylate) monolith/aminated graphene oxide composite (MAC) was prepared on the surface of stainless steel wire and employed as the extraction phase of SPME. After that, the MAC-based fiber and a stainless steel wire were connected to a DC power supply that allowed the implement of variable electric fields during adsorption and desorption processes. Various key factors influencing the extraction performance were inspected in detailed. Results well evidenced that the exertion of electric fields improved the enrichment performance, accelerated the trap and release procedures. The proposed MAC/EFA-SPME-HPLC-MS/MS method achieved wide linear ranges (0.005-50.0 µg/L), low limits of detection (0.54-1.3 ng/L) and good precision (2.7-7.0%) for the quantification of PCAHs. The related extraction mechanism was deduced. Additional, the current approach was successfully applied to monitor studied PCAHs at trace contents in environment waters, and the accuracy was confirmed by confirmatory experiments.

Circ_HECW2 regulates LPS-induced apoptosis of chondrocytes via miR-93 methylation.

INTRODUCTION: Circ_HECW2 plays a key role in lipopolysaccharide (LPS)-induced signal transduction, which is critical in osteoarthritis (OA). Thus, we analyzed the role of Circ_HECW2 in osteoarthritis. METHODS: The expression of Circ_HECW2 and miR-93 was examined using reverse-transcription polymerase chain reaction. Cell apoptosis was evaluated using Annexin V-FITC Apoptosis Detection Kit. RESULTS: Circ_HECW2 and miR-93 were inversely correlated, with Circ_HECW2 upregulated and miR-93 downregulated in OA and LPS-induced chondrocytes. Circ_HECW2 overexpression inhibited miR-93 expression and increased methylation of miR-93 coding gene. Cell apoptosis analysis showed that Circ_HECW2 overexpression increased LPS-induced chondrocyte apoptosis, while MiR-93 overexpression reversed the effects of Circ_HECW2 on chondrocyte apoptosis. CONCLUSION: In summary, our data revealed that the Circ_HECW2 is highly expressed in OA and might inhibit miR-93 expression through methylation to affect LPS-induced chondrocyte apoptosis.

A Bone-Hamstring Autograft for Arthroscopic Anterior Cruciate Ligament Reconstruction.

We describe a bone-hamstring autograft for anterior cruciate ligament reconstruction (ACLR). The semitendinosus and gracilis tendons are harvested using an open tendon stripper, keeping these distal tibial insertions intact. The bone-hamstring autograft is harvested using an oscillating saw. This modified autograft has the following advantages: (1) It possesses the potential for healing with the femur owing to its bone plug; (2) it is perfectly suited for various single-bundle reconstruction methods including oval-tunnel and rectangular-tunnel ACLR, as well as other flat ACLR methods; and (3) it is an attractive option for both primary ACLR and revision ACLR owing to its unique characteristics.

Easy fabrication of aminated graphene oxide functionalized magnetic nanocomposite for efficient preconcentration of phenolic acids prior to HPLC determination: Application in tea-derived wines.

In this study, aminated graphene oxide functionalized magnetic nanocomposite (AGMN) was facilely synthesized by one-pot hydrothermal approach and acted as the extraction phase of magnetic solid phase extraction (MSPE) of phenolic acids (PAs). Characterization results revealed that the AGMN possessed satisfying saturation magnetism and abundant functional groups. Under the optimal extraction parameters, the proposed AGMN/MSPE presented high enrichment capability to PAs. Sensitive and dependable method for measurement of PAs in wine was proposed by the combination of AGMN/MSPE and HPLC/DAD. Limits of detection and limits of quantification were in the ranges of 0.031-0.23 µg/L and 0.10-0.78 µg/L, respectively, and the RSDs for approach precision varied from 1.8% to 8.9%. Recoveries at low, medium and high fortified levels varied from 84.6% to 116%. The suggested method was used to quantify investigated PAs in ten kinds of Tieguanyin tea-derived wines, and found the contents of PAs in wines were related to the quality of tea-leaves and alcohol content.

Task specific monolith for magnetic field-reinforced in-tube solid phase microextraction of mercury species in waters prior to online HPLC quantification.

In this study, a novel sorbent based on task specific monolith doped with Fe3O4 was in situ fabricated in capillary and acted as the extraction medium of magnetic field-reinforced in-tube solid phase microextraction (MFR/IT-SPME) to trap and preconcentrate mercury species which were coordinated with dithizone to form chelates. Various characterization technologies evidenced that the obtained monolithic adsorbent presented porous and super paramagnetic properties, and possessed abundant functional groups. Results evidenced that the implementation of magnetic field during extraction stages enhanced the extraction efficiency of studied Hg chelates from 48.5% to 75.3% to 69.9-94.4%. Under the optimized extraction parameters, the introduced MFR/IT-SPME was online coupled to HPLC/DAD to quantify mercury species at ultra-trace levels in various water samples. Limits of detection varied from 0.0067 µg/L to 0.016 µg/L, and the RSDs for precision were below 7.5%. Additionally, related extraction mechanism was deduced and revealed multiple forces co-contributed to the enrichment. The reliability and accuracy of suggested online approach for speciation analysis of mercury was well proved by confirmatory experiments.

Preparation of a novel monolith-based adsorbent for solid-phase microextraction of sulfonamides in complex samples prior to HPLC-MS/MS analysis.

Effective extraction is an essential step in the sensitive and accurate analysis of sulfonamides (SAs) in complex samples. In this study, based on the chemical properties of SAs, a novel monolith-based adsorbent using 4-vinylbenzoic acid and 4-vinylphenylboronic acid as dual-functional monomers was tailored and employed as efficient extraction phase of solid-phase microextraction. Various characterized techniques were applied to investigate the structure and morphology of the obtained adsorbent. Due to the abundant functional groups, the synthetic adsorbent displayed satisfying extraction performance for target SAs through multiple interactions including ion-exchange, B-N coordination, π-π and hydrophobic interactions. Following elution with the desorption solution of methanol/formic acid (98.5/1.5, v/v), the extractive SAs were measured by HPLC-MS/MS. Under the optimized conditions, the proposed approach exhibited wide linear ranges (0.005-10.0 µg/L for most of analytes), low limits of detection (in the range of 0.31-2.3 ng/L) and good precision (RSDs were lower than 8.0%). In the analysis of target SAs in environment waters and honey samples, the recoveries at low, medium and high spiked concentrations were in the range of 83.5-119%, and the RSDs (n = 3) varied from 0.6% to 9.6%. Compared with existing approaches, the current method presents some merits such as high sensitivity, good reproducibility, low consumptions of sample and organic solvent.

Facile fabrication of functional groups-rich sorbent for the efficient enrichment of aromatic N- and S-containing compounds in environmental waters.

Extraction strategy is designed for the pretreatment of low contents of aromatic N- and S-containing compounds (ANSCs) in environmental waters prior to chromatographic analysis. To enrich studied ANSCs effectively, poly (9-vinylanthracene/4-vinylphenylboronic acid-co-ethylene dimethacrylate/divinylbenzene) polymeric monolithic sorbent were facilely fabricated using the one-step free radical polymerization. Various technologies were employed to investigate the structure and morphology of the resultant monolith. Combining with solid-phase microextraction format, the sorbent exhibited satisfying concentrated performance for ANSCs through multiply interactions under the optimized conditions. After desorption with eluent, the retained analytes were analyzed by HPLC. Results showed that the extraction efficiencies ranged from 51.6 to 93.2%. The linear ranges and limits of detection were 0.01-150 µg/L and 0.63-2.64 ng/L, respectively. Furthermore, the precisions were all below 10%. The introduced approach was productively practiced on three real water samples for simultaneous quantification of studied ANSCs, and the fortified recoveries ranged from 81.5 to 118%. All the results well evidenced that prepared sorbent can enrich ANSCs effectively and the introduced method is reliable alternative for routine analysis of ANSCs in environmental waters.

Natural ingredients-derived antioxidants attenuate H2O2-induced oxidative stress and have chondroprotective effects on human osteoarthritic chondrocytes via Keap1/Nrf2 pathway.

Osteoarthritis (OA) is the most common disabling joint disease and its pathological process is closely related to oxidative stress. Recent studies have shown that antioxidants allicin, sulforaphane, and lycopene derived from natural ingredients garlic, broccoli, and tomato can reduce the degree of oxidative stress and the expression of inflammatory markers, indicating that theses antioxidants might be helpful for OA treatment. In this study, we investigated the effects of allicin, sulforaphane, and lycopene on H2O2-stimulated human osteochondral samples and osteoarthritic chondrocytes. Our results revealed that allicin, sulforaphane, and lycopene effectively reduced the oxidative stress-induced cell apoptosis, and increased gene expression of antioxidant enzymes. Besides, these natural ingredients-derived antioxidants reduced the expression of inflammatory factors, enhanced the chondrogenic matrix synthesis, and reduced the hypertrophic differentiation of osteoarthritic chondrocytes. These regulations were mainly through the activation of Keap1/Nrf2 pathway. Our findings suggest that these antioxidants might be a potential therapeutic strategy for OA.

FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice.

OBJECTIVES: This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis. METHODS: Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and µCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis. RESULTS: R3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice. CONCLUSIONS: Our study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.

The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1ß production of macrophages and aggravated synovitis in osteoarthritis.

Synovitis, a common clinical symptom for osteoarthritis (OA) patients, is highly related to OA pathological progression and pain manifestation. The activated synovial macrophages have been demonstrated to play an important role in synovitis, but the mechanisms about macrophage activation are still not clear. In this study, we found that the exosome-like vesicles from osteoarthritic chondrocytes could be a new biological factor to stimulate inflammasome activation and increase mature IL-1ß production in macrophages. The degraded cartilage explants produced more exosome-like vesicles than the nondegraded ones, while the exosome-like vesicles from chondrocytes could enter into joint synovium tissue and macrophages. Moreover, the exosome-like vesicles from osteoarthritic chondrocytes enhanced the production of mature IL-1ß in macrophages. These vesicles could inhibit ATG4B expression via miR-449a-5p, leading to inhibition of autophagy in LPS-primed macrophages. The decreased autophagy promoted the production of mitoROS, which further enhanced the inflammasome activation and subsequent IL-1ß processing. Ultimately, the increase of mature IL-1ß may aggravate synovial inflammation and promote the progression of OA disease. Our study provides a new perspective to understand the activation of synovial macrophages and synovitis in OA patients, which may be beneficial for therapeutic intervention in synovitis-related OA patients.