Knee Joint Tissues Research Articles

Screening and analysis for autophagy-related lncRNA in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Long non-coding RNA (lncRNA) has become a key epigenetic regulator that regulates gene expression and affects a variety of biological processes. LncRNA plays an important role in the occurrence and development of rheumatoid arthritis (RA). The study on lncRNA in peripheral blood cells of RA patients has been reported. However, there is no study on autophagy regulation by lncRNA in RA patients. This study aims to provide a new direction for the diagnosis and treatment of RA via screening the changes of lncRNAs in RA fibroblast-like synoviocytes (RA-FLSs) before and after autophagy and finding the key lncRNAs targeting RA-FLSs autophagy. Synovial tissues of 6 RA patients after knee and hip joint surgery were obtained, and RA-FLSs were cultured to the 5th generation for further experiments (tissue culture method). After treatment with mTOR inhibitor PP242, the expression of LC3-II was detected by Western blotting. Total RNAs of 3 cases of RA-FLSs before and after treatment with mTOR inhibitor PP242 were extracted by TRIzol and screened by Agilent Human ceRNA Microarray 2019 (4×180 K, design ID: 086188) chip. The lncRNAs with significantly changed expression levels were selected (difference multiple≥2.0, P<0.05). Bioinformatics technology was used to analyze the gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the differentially expressed lncRNAs, and to explore the possible role of differentially expressed lncRNAs in the pathogenesis of RA. Subsequently, ENST00000584721.1 and ENST00000615939.1 were identified in all the 6 samples of RA-FLSs using real-time RT-PCR, which were selected by previous chip screen combined with GO enrichment analysis and KEGG analysis. RA-FLSs were successfully isolated and cultured from the synovial tissues of the patient's knee or hip joint. After 6 RA-FLSs were treated with PP242, the expression level of autophagy marker protein LC3-II was increased (P<0.05). PP242 induced autophagy in RA-FLSs. LncRNA sequencing analysis showed that a total of 591 lncRNAs were significantly changed, of which 428 were up-regulated and 163 were down-regulated.Go analysis showed that these differentially expressed lncRNAs were associated with negative regulation of Th17 function, T cell related cytokines production, and TGF-β receptor signaling pathway, as well as IL-6 receptor complex formation and type I TGF-β receptor binding. KEGG analysis showed that autophagy pathway, TGF-β, TNF-α, IL-17 signaling pathway, and Th17, Th1, Th2, osteoclast differentiation pathway were the most abundant signal pathways of differentially expressed lncRNAs during autophagy. The expression of ENST00000584721.1 was up-regulated (P<0.05) and the expression ofENST00000615939.1 was down-regulated (P<0.05) in RA-FLSs undergoing autophagy, by using real-time RT-PCR validation which was in consistent with the microarray results. The reliability of microarray screening differential genes was confirmed. GO analysis showed that ENST00000584721.1 and ENST00000615939.1 were related to ribosome transport and autophagy assembly, respectively. KEGG analysis showed that ENST00000584721.1 was related to mitogen-activated protein kinase (MAPK) signaling pathway, and ENST00000615939.1 was related to FoxO signaling pathway. Differentially expressed lncRNAs in RA-FLSs have been identified with microarray analysis. In RA, differential expression of lncRNAs is involved in the autophagy of RA-FLSs. The underlying mechanisms based on bioinformatics analysis include regulating the secretion of cytokines, such as IL-6, TGF-β, TNF-α and IL-17, participating in the immune cell differentiation, such as Th17, Th1, Th2 cells and osteoclasts, as well as regulating the autophagy pathway, MAPK, FoxO, and other signaling pathways. It has been verified that the expression of ENST0000584721.1 is up-regulated and ENST0000615939.1 is down-regulated after autophagy of RA FLSs, which provides a good experimental basis for further study on the mechanism of lncRNA in RA-FLSs autophagy.

Effects of Dipsacus asperoides and Phlomis umbrosa Extracts in a Rat Model of Osteoarthritis.

The implementation of the Nagoya Protocol highlighted the importance of identifying alternative herbal products that are as effective as traditional medicine. Dipsacus asperoides and Phlomis umbrosa, two species used in the Korean medicine ‘Sok-dan’, are used for the treatment of bone- and arthritis-related diseases, and they are often mixed or misused. To identify herbal resources with similar efficacy, we compared the effects of D. asperoides extract (DAE) and P. umbrosa extract (PUE) on osteoarthritis (OA) in a monosodium iodoacetate (MIA)-induced OA rat model. Weight-bearing distribution, serum cytokines, histopathological features, and the expression of matrix metalloproteinases (MMPs) of knee joint tissues were examined in the OA rats treated with DAE and PUE (200 mg/kg) for 21 days. DAE and PUE restored weight-bearing distribution, inhibited the production of serum cytokines, and alleviated the histopathological features of the OA knee tissue. DAE or PUE treatment decreased OA-induced overexpression of MMP-2, MMP-9, and MMP-13 in the knee joint tissue. This study demonstrated the efficacy of both DAE and PUE in an MIA-induced OA model, providing a basis for the clinical use of these products in traditional Korean medicine.

Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis.

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c-fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion.

Osteoarthritis (OA) is the most common arthritis with a rapidly increasing prevalence. Disease progression is irreversible, and there is no curative therapy available. During OA onset, abnormal mechanical loading leads to excessive osteoclastogenesis and bone resorption in subchondral bone, causing a rapid subchondral bone turnover, cyst formation, sclerosis, and finally, articular cartilage degeneration. Moreover, osteoclast-mediated angiogenesis and sensory innervation in subchondral bone result in abnormal vascularization and OA pain. The traditional Chinese medicine Panax notoginseng (PN; Sanqi) has long been used in treatment of bone diseases including osteoporosis, bone fracture, and OA. In this study we established two-dimensional/bone marrow mononuclear cell/cell membrane chromatography/time of flight mass spectrometry (2D/BMMC/CMC/TOFMS) technique and discovered that diterbutyl phthalate (DP) was the active constituent in PN inhibiting osteoclastogenesis. Then we explored the therapeutic effect of DP in an OA mouse model with anterior cruciate ligament transaction (ACLT). After ACLT was conducted, the mice received DP (5 mg·kg-1·d-1, ip) for 8 weeks. Whole knee joint tissues of the right limb were harvested at weeks 2, 4, and 8 for analysis. We showed that DP administration impeded overactivated osteoclastogenesis in subchondral bone and ameliorated articular cartilage deterioration. DP administration blunted aberrant H-type vessel formation in subchondral bone marrow and alleviated OA pain assessed in Von Frey test and thermal plantar test. In RANKL-induced RAW264.7 cells in vitro, DP (20 μM) retarded osteoclastogenesis by suppressing osteoclast fusion through inhibition of the ERK/c-fos/NFATc1 pathway. DP treatment also downregulated the expression of dendritic cell-specific transmembrane protein (DC-STAMP)and d2 isoform of the vacuolar (H+) ATPase V0 domain (Atp6v0d2) in the cells. In conclusion, we demonstrate that DP prevents OA progression by inhibiting abnormal osteoclastogenesis and associated angiogenesis and neurogenesis in subchondral bone.

Glucosamine and Chondroitin Sulfate: Is There Any Scientific Evidence for Their Effectiveness as Disease-Modifying Drugs in Knee Osteoarthritis Preclinical Studies?-A Systematic Review from 2000 to 2021.

Simple SummaryOsteoarthritis is the most common progressive joint disease diagnosed in companion animals and its management continues to be a significant challenge. Nutraceuticals have been widely investigated over the years in the treatment of osteoarthritis and among them, glucosamine and chondroitin sulfate treatments are probably the most common therapies used in veterinary management. However, heterogeneous results were obtained among animal studies and the evidence of their efficacy is still controversial. Animal models have a crucial role in studying the histological changes and evaluating the therapy efficacy of different drugs. Consequently, we consider it may be of interest to evaluate the effectiveness of the most representative nutraceuticals in experimental animal studies of osteoarthritis. In this systematic review, we found a large inconsistency among the experimental protocols, but a positive cartilage response and biochemical modulation were observed in half of the evaluated articles, mainly associated with pre-emptive administrations and with some therapies’ combinations. Even though some of these results were promising, additional data are needed to draw solid conclusions, and further studies evaluating their efficacy in the long term and focusing on other synovial components may be needed to clarify their function.Glucosamine and chondroitin sulfate have been proposed due to their physiological and functional benefits in the management of osteoarthritis in companion animals. However, the scientific evidence for their use is still controversial. The purpose of this review was to critically elucidate the efficacy of these nutraceutical therapies in delaying the progression of osteoarthritis, evaluating their impact on the synovial knee joint tissues and biochemical markers in preclinical studies by systematically reviewing the last two decades of peer-reviewed publications on experimental osteoarthritis. Three databases (PubMed, Scopus and, Web of Science) were screened for eligible studies. Twenty-two articles were included in the review. Preclinical studies showed a great heterogeneity among the experimental designs and their outcomes. Generally, the evaluated nutraceuticals, alone or in combination, did not seem to prevent the subchondral bone changes, the synovial inflammation or the osteophyte formation. However, further experimental studies may be needed to evaluate their effect at those levels. Regarding the cartilage status and biomarkers, positive responses were identified in approximately half of the evaluated articles. Furthermore, beneficial effects were associated with the pre-emptive administrations, higher doses and, multimodality approaches with some combined therapies. However, additional studies in the long term and with good quality and systematic design are required.

Knockdown of hsa_circ_0134111 alleviates the symptom of osteoarthritis via sponging microRNA-224-5p

ABSTRACT The relevance of circular RNAs (circRNAs) has been indicated in the progression of various diseases. Nevertheless, the precise function of circRNAs in osteoarthritis (OA) remains to be established. Therefore, we aimed to investigate changes in the expression of a specific circRNA, hsa_circ_0134111 (circ_PDE1C) and predict its functions in OA. A rat model of OA was constructed to detect circ_PDE1C expression in knee joint tissues. Subsequently, CHON-001 chondrocytes were treated with IL-1β to mimic OA in vitro. circ_PDE1C was significantly overexpressed in knee cartilage tissues from OA patients relative to amputation patients. Knockdown of circ_PDE1C inhibited extracellular matrix (ECM) degradation and chondrocyte apoptosis. Furthermore, circ_PDE1C could target miR-224-5p, and miR-224-5p expressed poorly in knee cartilage tissues from OA patients. Overexpression of miR-224-5p inhibited ECM degradation and apoptosis in chondrocytes. miR-224-5p also targeted CCL2, which activated the JAK2/STAT signaling pathway, thereby promoting cartilage degradation and exacerbating the symptoms of OA patients. In conclusion, our findings underscore a novel role of circ_PDE1C in OA pathogenesis and suggest that targeting circ_PDE1C/miR-224-5p/CCL2 axis might provide an attractive approach for OA therapy.

Cathepsin-B involved in effect of electroacupuncture by inhibiting the activation of NLRP3 inflammasome in rats with acute gouty arthritis

To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA. A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg-1·d-1), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1β(IL-1β) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score，the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1β,IL-18 were significantly increased (P<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1，IL-1β,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (P<0.01, P<0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (P<0.05). EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.

Status and treatment of knee extension device disruption after total knee arthroplasty

To summarize the principle, classification, and treatment methods of knee extension device disruption after total knee arthroplasty (TKA). By extensively consulted the relevant domestic and abroad literature, the principle, classification, and treatment methods of injury according to different parts of the knee extension device after TKA were summarized and analyzed. The knee extension device disruption after TKA mainly occurs in the quadriceps tendon, patella tendon, and patella. Once the knee extension device is injured, it will seriously affect the functional recovery of the patient after surgery, resulting in delayed knee extension, limited range of motion, difficulty walking, and joint pain, etc. The current treatment methods are diverse, including conservative treatment and surgical treatment. Surgical treatment includes direct suture repair (traditional perosseous fixation and suture anchoring techniques), reconstruction and reinforcement repair (reconstruction using synthetic patches, autografts, and allografts). For the treatment of different parts, it is necessary to comprehensively consider the patient's knee joint tissue condition, the presence or absence of underlying diseases, and the presence or absence of donors. There is no uniform conclusion on the treatment of knee extension device disruption after TKA. Different injury situations need to be considered comprehensively to choose the appropriate treatment method.

Upregulated endonuclease Regnase-1 suppresses osteoarthritis by forming a negative feedback loop of catabolic signaling in chondrocytes

BackgroundRibonucleases (RNases) play central roles in the post-transcriptional regulation of mRNA stability. Our preliminary results revealed that the endonuclease Regnase-1 is specifically upregulated in osteoarthritic chondrocytes. We herein explored the possible functions and regulatory mechanisms of Regnase-1 in a mouse model of osteoarthritis (OA).MethodsThe expression and target genes of Regnase-1 were identified by microarray analysis in primary-culture mouse articular chondrocytes. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM). The function of Regnase-1 in DMM-induced post-traumatic OA mice was examined by adenovirus-mediated overexpression or knockdown in knee joint tissues, and also by using Regnase-1 heterozygous knockout mice (Zc3h12a+/−).ResultsAmong the RNases, Regnase-1 was exclusively upregulated in chondrocytes stimulated with OA-associated catabolic factors. Adenovirus-mediated overexpression or knockdown of Regnase-1 alone in joint tissues did not cause OA-like changes. However, overexpression of Regnase-1 in joint tissues significantly ameliorated DMM-induced post-traumatic OA cartilage destruction, whereas knockdown or genetic ablation of Regnase-1 exacerbated DMM-induced cartilage destruction. Mechanistic studies suggested that Regnase-1 suppresses cartilage destruction by modulating the expression of matrix-degrading enzymes in chondrocytes.ConclusionOur results collectively suggest that upregulated Regnase-1 in OA chondrocytes may function as a chondro-protective effector molecule during OA pathogenesis by forming a negative feedback loop of catabolic signals, such as matrix-degrading enzyme expression, in OA chondrocytes.

Effects of Angular Resolution and b Value on Diffusion Tensor Imaging in Knee Joint

To investigate the influences of the diffusion gradient directions (angular resolution) and the strength of the diffusion gradient (b value) on diffusion tensor imaging (DTI) metrics and tractography of various connective tissues in knee joint. Two rat knee joints were scanned on a preclinical 9.4-T system using a 3-dimensional diffusion-weighted spin echo pulse sequence. One protocol with b value of 500, 1500, and 2500 s/mm2 were acquired separately using 43 diffusion gradient directions. The other protocol with b value of 1000 s/mm2 was performed using 147 diffusion gradient directions. The in-plane resolution was 45 µm isotropic. Fractional anisotropy (FA) and mean diffusivity (MD) were compared at different angular resolution. Tractography was quantitatively evaluated at different b values and angular resolutions in cartilage, ligament, meniscus, and growth plate. The ligament showed higher FA value compared with growth plate and cartilage. The FA values were largely overestimated at the angular resolution of 6. Compared with FA, MD showed less sensitivity to the angular resolution. The fiber tracking was failed at low angular resolution (6 diffusion gradient directions) or high b value (2500 s/mm2). The quantitative measurements of tract length and track volume were strongly dependent on angular resolution and b value. To obtain consistent DTI outputs and tractography in knee joint, the scan may require a proper b value (ranging from 500 to 1500 s/mm2) and sufficient angular resolution (>14) with signal-to-noise ratio >10.

Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice.

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.

Double-dose cefuroxime concentrations in bone, synovial fluid of the knee joint and subcutaneous adipose tissue–A randomised porcine microdialysis study

This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3000 mg (Group 1) or two single 15 min infusions of 1500 mg administered 4 h apart (Group 2). Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4 μg/mL. The mean time fT>MIC (4 μg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4 μg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p = 0.053). Within 50 min after administration, the mean concentration of 4 μg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 μg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero). During an 8 h interval, double-dose cefuroxime administered as 2 × 1500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 μg/mL) than a single bolus of 3000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1500 mg) should be considered 3 h after the first administration.

Surgical treatment of skeletal metastases in proximal tibia: a multicenter case series of 74 patients

Background and purpose — The proximal tibia is a rare site for metastatic bone disease and is a challenging anatomical site to manage due to the proximity to the knee joint and poor soft tissue envelope. We investigated implant survival and complications of different surgical strategies in the treatment of proximal tibia pathological fractures. Patients and methods — The study comprised a 4 medical center, retrospective analysis of 74 patients surgically treated for metastases of the proximal tibia. Patient records were reviewed to identify outcome, incidence, and type of complications as well as contributing factors. Results — Reconstruction techniques comprised cement-augmented osteosynthesis (n = 33), tumor prosthesis (n = 31), and total knee arthroplasty with long cemented stems (n = 10). Overall implant survival was 88% at 6 months and 1 year, and 67% at 3 years. After stratification by technique, the implant survival was 82% and 71% at 1 and 3 years with tumor prosthesis, 100% at 1 and 3 years with total knee arthroplasty, and 91% at 1 year and 47% at 3 years with osteosynthesis. Preoperative radiotherapy decreased implant survival. Complications were observed in 19/74 patients. Treatment complications led to amputation in 5 patients. Interpretation — In this study, the best results were seen with both types of prothesis reconstructions, with good implant survival, when compared with treatment with osteosynthesis. However, patients treated with tumor prosthesis showed an increased incidence of postoperative infection, which resulted in poor implant survival. Osteosynthesis with cement is a good alternative for patients with short expected survival whereas endoprosthetic replacement achieved good medium-term results.

Gadolinium retention within multiple rat organs after intra-articular administration of gadolinium-based contrast agents

ObjectiveTo characterize the extent of retention and biodistribution of gadolinium (Gd) following intra-articular (IA) injection of linear and macrocyclic gadolinium-based contrast agents (GBCAs) into the knee joint of a rat model.Materials and methodsFifteen Wistar rats were divided into five groups and underwent fluoroscopically-guided injections of both knee joints of (1) clinical 1:200 dilution (low dose, LD) gadodiamide (linear GBCA), (2) LD gadobutrol (macrocyclic GBCA), (3) undiluted (high dose, HD) gadodiamide, (4) HD gadobutrol, and (5) saline. Gd concentrations were quantified by inductively coupled plasma mass spectrometry in (1) blood and urine samples obtained over a 72 h period and (2) knee joint tissues, brain, kidney, and bone marrow at 3 days post-injection.ResultsBoth HD and LD gadodiamide and gadobutrol were rapidly absorbed from the joint with peak serum and urine concentration at 1 h post-injection, with relatively faster clearance of gadobutrol. All GBCA-exposed groups had detectable levels of Gd in the joint tissues, bone marrow, and/or kidneys (median tissue gadolinium range: 0.1–71 μg Gd/g tissue), with higher amounts observed with gadodiamide versus gadobutrol. Retention within brain tissues was only detected following HD gadodiamide administration but not LD gadodiamide nor HD or LD gadobutrol.ConclusionThere was rapid systemic absorption, redistribution, and widespread multi-organ retention of Gd following IA injection of both linear and macrocyclic GBCAs, despite substantial amounts of urinary excretion. Higher concentrations of Gd were observed with administration of gadodiamide compared to gadobutrol in most tissues and biofluids.

Occurrence of mercury in the knee joint tissues

Introduction: Mercury is one of the elements that are commonly found in nature. This element is highly toxic, mainly affecting the nervous system, kidneys and lungs. Mercury ions can accumulate in bone and cartilage and build up behind calcium ions in carbonates and hydroxyapatites. High mercury concentrations in the spongy bone compared to the compacted bone were found. Aim: The aim of the manuscript was to assess the mercury content in tibial and femoral tissue taken from patients undergoing knee arthroplasty. Material and methods: Samples were taken from 17 patients (tibial and femoral bone samples), collected from patients who underwent knee arthroplasty. The tested samples were homogenized and determined by atomic absorption spectrometry and the AMA 254 amalgamation technique. Studies have shown mercury presence in all samples tested. Results and discussion: The range of mercury content in the tested samples was 3.3–19.18 μg/kg. The average for the examined bone tissue samples was 8.71 μg/kg, while for the tibia it was slightly higher (9.08 μg/kg), compared to the femur (8.34 μg/kg). There was a high mercury content in men’s bone tissue (10.05 μg/kg), compared to women (8.15 μg/kg). In both sexes, higher levels of mercury in the tibia were found in men (11.08 μg/kg in men, and 8.24 μg/kg in women). Conclusions: The dependence between mercury concentration in bone tissue and the patient’s age, weight and BMI, the number of cigarettes smoked and the consumption of fish and seafood were checked. There were no statistically significant correlations between these indicators.

RETRACTED: Inhibited microRNA-218-5p attenuates synovial inflammation and cartilage injury in rats with knee osteoarthritis by promoting sclerostin

In recent decades, the role of microRNAs (miRNAs) in human diseases has been widely studied. This research is designed to explore the effect of miR-218-5p on knee osteoarthritis (KOA) progression in a rat model with the involvement of sclerostin (SOST). The KOA rat models were constructed by Hulth method, and then were classified into the KOA, miR-218-5p inhibitor, inhibitor negative control (NC), overexpressed (OE)-SOST, OE-NC, miR-218-5p inhibitor + si-SOST, or miR-218-5p inhibitor + si-NC group. The pathological changes of rats' synovial tissues were observed; the apoptosis in rat synovial tissues was assessed; levels of IL-1β, TNF-α, PGE2 and COX-2 in serum and synovial tissues, along with SOD and MDA contents in synovial tissues were determined. The morphological changes in cartilage tissues were observed. MMP-13 and Col II expression in cartilage tissues was assessed; expression of β-catenin and Col2A1 in cartilage tissues was assessed. miR-218-5p and SOST expression in rat knee joint tissues was assessed. KOA rats had increased miR-218-5p expression and decreased SOST expression. MiR-218-5p targeted SOST. Rats injected with miR-218-5p inhibitor and OE-SOST had alleviated pathological changes, reduced TUNEL positive cell rate, decreased serum contents of IL-1β, TNF-α, PGE2, COX-2 and MDA, and increased SOD activity in synovial tissues, alleviated pathological changes, enhanced Col II positive rate and reduced MMP-13 positive rate, decreased β-catenin expression and increased Col2A1 expression in cartilage tissues. The miR-218-5p inhibition could attenuate synovial inflammation and cartilage injury in KOA rats by promoting SOST, which may be helpful for KOA treatment.

Effects of Catalpa Alcohol From Rehmannia glutinosa on Calcium-Binding Protein, Interleukin-1β, and Galectin-3 in Synovial Tissues of Rats With Knee Osteoarthritis

Objectives We aimed to evaluate the effects of catalpa alcohol from Rehmannia glutinosa on the expressions of calcium-binding protein (S100A12), interleukin-1β (IL-1β), and galectin-3 in the synovium of rats with early knee osteoarthritis (KOA). Methods Fifty-two adult male Wistar rats aged 3 to 8 weeks were divided into normal control (n = 16), model (n = 12), low-dose (n = 12), and high-dose groups (n = 12). On the 10th day after modeling, 6 rats in normal control group and 6 in the other 3 groups were randomly selected. X-ray and 3-dimensional computed tomography (3D CT) images of the left knee joint were taken under live anesthesia. The joint cavity of sacrificed rats was opened to observe cartilage surface. After 28 consecutive days of administration, the synovial tissue of left knee joint was collected. Results The S100A12, IL-1β, and galectin-3 levels in synovial tissue were detected by immunohistochemistry and ELISA. There were articular cartilage defects in left knees. Radiologic examination showed significant joint space narrowing and hyperplasia, and 3D CT joint space value decreased (P &amp;lt; 0.05). The Mankins and OARSI scores of synovial histopathology were significantly different (P &amp;lt; 0.05). The S100A12, IL-1β, and galectin-3 levels in synovial tissue of the model group significantly exceeded those of the normal control group (P &amp;lt; 0.01). Compared with the model group, such levels of low-dose (P &amp;lt; 0.05) and high-dose groups (P &amp;lt; 0.01) were significantly lower. Conclusions The S100A12, IL-1β and galectin-3 levels in synovium tissue decreased with rising concentration of catalpa alcohol from R. glutinosa. Therefore, this drug is potentially suitable for inhibiting an inflammatory response to delay the progression of KOA.

Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1β induction and to assess responsiveness of the explants. Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. Methylprednisolone. The samples were allocated into six groups: (1) control, (2) MPA (10-3M), (3) MPA (10-4M), (4) IL1β, (5) IL1β + 10-3M MPA, or (6) IL1β + 10-4M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1β (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFβ1, TLR4, and adipose-related molecules. Methylprednisolone significantly mitigated IL1β induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.

TRIM24-RIP3 axis perturbation accelerates osteoarthritis pathogenesis

ObjectivesRecently, necroptosis has attracted increasing attention in arthritis research; however, it remains unclear whether its regulation is involved in osteoarthritis (OA) pathogenesis. Since receptor-interacting protein kinase-3 (RIP3) plays a pivotal...

Analysis on the expression and value of CCL2 and CCL3 in patients with osteoarthritis

In this study, we investigated the clinical value of CC chemokine ligand 2 (CCL2) and CC chemokine ligand 3 (CCL3) in osteoarthritis (OA). A prospective analysis was performed on 126 patients with rheumatoid arthritis of the knee (observation group (OG)) who admitted to Qilu hospital from August 2016 to August 2018 and 135 healthy controls (control group (CG)) who underwent physical examinations during the same period. The concentrations of CCL2 and CCL3 in peripheral blood were compared between the two groups, and the predictive value of the two on the occurrence, efficacy and prognosis of recurrence of OA were analyzed. In addition, an OA rat model was established to detect the relative protein levels of CCL2 and CCL3 in rat knee joint tissues. There were no statistically significant differences between the two groups in baseline data such as age, body mass index (BMI), gender, smoking, drinking, educational level, family medical history and living environment (P > 0.05). CCL2 and CCL3 increased in peripheral blood of patients in the OG (P < 0.05), both of which were positively correlated with rheumatoid factor (RF) (P < 0.001). CCL2 and CCL3 were of good predictive value for the occurrence, efficacy and prognosis of recurrence of OA (P < 0.001). The relative protein levels of CCL2 and CCL3 in bone and joint tissues of OA rats were significantly higher than those of normal rats (P < 0.001). CCL2 and CCL3 are elevated in peripheral blood of OA patients, which have good predictive value for the occurrence, efficacy and prognosis of recurrence of OA, indicating their potential roles as excellent markers for diagnosis and treatment of OA in the future.