Chronic Joint Disease Research Articles

Effects of Growth Hormone on Osteoarthritis Development.

Osteoarthritis (OA), a chronic joint disease characterized by primary or secondary degeneration of articular cartilage and bone dysplasia, is associated with various risk factors and is the leading cause of musculoskeletal pain and disability, severely impacting the quality of life. Growth hormone (GH), secreted by the anterior pituitary gland, is essential in mediating the growth and development of bone and cartilage. Reportedly, osteoarthritis increases, and the growth hormone decreases with age. A negative correlation between GH and OA suggests that GH may be related to the occurrence and development of OA. Considering that abnormal growth hormone levels can lead to many diseases related to bone growth, we focus on the relationship between GH and OA. In this review, we will explain the effects of GH on the growth and deficiency of bone and cartilage based on the local pathological changes of osteoarthritis. In addition, the potential feasibility of treating OA with GH will be further explored and summarized.

Transcutaneous auricular vagus nerve stimulation mitigates gouty inflammation by reducing neutrophil infiltration in BALB/c mice

Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation.

Chronic rhinosinusitis with osteomyelitis in a geriatric snow leopard (Panthera uncia)

AbstractA geriatric, 16‐year‐9‐month‐old, male snow leopard (Panthera uncia) under human care was necropsied after euthanasia over concerns for worsening chronic kidney disease and bilateral blindness. Gross and histological examinations revealed necrotising frontal sinusitis and osteomyelitis with mixed‐cellular rhinotracheitis, affecting the right frontal sinus, right nasal cavity and trachea, respectively, with intralesional and cilia‐associated Gram‐negative bacilli detected. Microbiological cultures were inconclusive, although Bordetella bronchiseptica and feline herpesvirus 1 were positive on PCR analysis. Immunohistochemistry, however, refuted active feline herpesvirus 1 involvement. Marked, chronic, bilateral, renal degeneration and fibrosis (chronic kidney disease), mild hepatic cirrhosis, bilateral chronic degenerative stifle joint disease and testicular intratubular seminoma were also detected on postmortem examination. No gross ocular or optic nerve lesions were identified; however, histology indicated bilateral diffuse outer retinal atrophy and retinal detachment, supportive of clinical blindness at time of death. This case represents the first report of chronic rhinosinusitis and osteomyelitis in a snow leopard.

Therapeutic Effects of Puerarin Loaded Bone Marrow Mesenchymal Stem Cell-Derived Exosomes in a Rat Model of Osteoarthritis.

Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. The primary objective of this study was to assess the therapeutic potential of puerarin loaded bone marrow mesenchymal stem cell-derived exosomes (Pue@BMSC-Exo), and reveal their inflammatory regulating mechanisms through affecting the nuclear factor kappa-B (NF-κB) signaling pathway. In this study, exosomes derived from BMSCs were isolated and identified. Cell proliferation and migration were evaluated by CCK-8 and scratch methods. Furthermore, histological and micro-computed tomography analysis were performed to assess alterations of articular cartilage in OA rats. Results showed that BMSC-Exo and Pue@BMSC-Exo conformed with the basic characteristics of exosomes. BMSC-Exo increased the solubility of Pue and enhanced drug uptake by chondrocytes. In addition, Pue@BMSC-Exo stimulated proliferation and migration of chondrocyte, and also promoted cartilage repair by reducing matrix metalloproteinase MMP13 production and increasing type II collagen (Col2) synthesis. Furthermore, Pue@BMSC-Exo, by effectively inhibiting the NF-κB signaling pathway, reduced the production of inflammatory mediators and attenuated the release of the inflammatory marker nitric oxide (NO), ultimately ameliorating the damage of chondrocyte. These findings exhibited the potential therapeutic significance of Pue@BMSC-Exo in OA and warranted further exploration in clinical applications.

Targeting Synovial Macrophages with Astaxanthin-Loaded Liposomes for Antioxidant Treatment of Osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease highly associated with an imbalance in the network of inflammatory factors and typically characterized by oxidative stress and cartilage damage. Moreover, the specificity of the joint structure makes it difficult for drugs to achieve good penetration and effective enrichment in the joint cavity. Therefore, therapeutic strategies that increase the specific targeting of drugs to inflammatory joint and incorporate antioxidative stress effects are important to improve the efficacy of OA. Here, we developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA) loaded with the antioxidant astaxanthin (AST) to enhance the water solubility and stability of AST and to target the delivery of AST to the site of OA, leading to a significant improvement in therapeutic efficacy. In vitro experiments demonstrated that, due to the recognition by FA of the receptor folate receptor β on the surface of activated macrophages, the cellular uptake efficiency of AST@Lip-FA was increased. Meanwhile, intracellularly overexpressed inflammatory mediators such as reactive oxygen species and nitric oxide were efficiently removed by AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA was precisely enriched in the inflamed joints and achieved long-term retention, fully utilizing the anti-inflammatory, antioxidant, and cartilage-protecting effects of AST to effectively alleviate the progression of OA. In summary, AST@Lip-FA has an important prospect as a potential and effective therapeutic strategy for OA.

Effect of Glucosamine Hydrochloride Combined with Celecoxib on Inflammatory Response and Bone Metabolism in Patients with Knee Osteoarthritis

Background: Knee osteoarthritis is one of the common chronic degenerative joint diseases. The present study explored the efficacy of glucosamine hydrochloride combined with celecoxib in the treatment of knee osteoarthritis and its effect on inflammatory response and bone metabolism. Material and Methods: Ninety patients with knee osteoarthritis were randomly divided into the single treatment group and the combined treatment group, which received the treatment using single glucosamine hydrochloride and glucosamine hydrochloride combined with celecoxib for three months, respectively. Results: After treatment, compared with the single treatment group, in the combined treatment group the total effective rate was increased, the Visual Analogue Scale score was decreased, the Lysholm score was increased, the serum tumor necrosis factor-α, interleukin 6 and interleukin 1β levels were decreased, the serum β-C-telopeptides of type I collagen level was decreased, and the serum bone-specific alkaline phosphatase and osteocalcin levels were increased. The incidence of adverse reactions during treatment had no significant difference between two groups. Conclusions: Glucosamine hydrochloride combined with celecoxib has a good therapeutic efficacy for patients with knee osteoarthritis, and it can improve the bone metabolism and reduce the inflammatory response in patients.

Alterations in Immune Parameters ADP, ANA, IL-1, IL-6, IL-8, STAT-4, and TNF Alpha in Patients with Rheumatoid Arthritis and Osteoarthritis

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic joint diseases with distinct pathophysiological mechanisms, but both involve alterations in immune parameters. This research investigates the alterations in several immune parameters, specifically adiponectin (ADP), antinuclear antibodies (ANA), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), signal transducer and activator of transcription 4 (STAT-4), and tumor necrosis factor-alpha (TNF Alpha), in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Also, the current study aims to identify the changes occurring in the physiological and immune parameters of people suffering from rheumatic diseases, as Evaluation of Immunological Inflammatory biomarkers levels ADP, ANA, IL1, IL6, IL8, STAT-4 and TNF-α. Material & Methods: A cross-sectional laboratory-based study with 90 patient’s participant was conducted. Using ELISA kits and laboratory tests, various biomarkers (Immunological Inflammatory biomarkers levels ADP, ANA, IL1, IL6, IL8, STAT-4 and TNF-α were measured among rheumatoid arthritis and Osteoarthritis patients. Results: The findings revealed elevated levels of IL-1, IL-6, IL-8, STAT-4, and TNF Alpha in RA patients, reflecting a heightened inflammatory state. In contrast, OA patients exhibited a more moderate increase in these parameters, suggesting differing immune activation pathways. ADP and ANA levels showed distinct variations between the two patient groups, indicating their potential roles in the pathogenesis and progression of RA and OA. Conclusion: These results contribute to a better understanding of the immune mechanisms underlying RA and OA, highlighting the importance of targeted therapeutic strategies to manage these conditions effectively. Further research is recommended to explore the clinical implications of these findings and develop personalized treatment approaches.

Identification of key hub genes in knee osteoarthritis through integrated bioinformatics analysis.

Knee osteoarthritis (KOA) is a common chronic joint disease globally. Synovial inflammation plays a pivotal role in its pathogenesis, preceding cartilage damage. Identifying biomarkers in osteoarthritic synovial tissues holds promise for early diagnosis and targeted interventions. Gene expression profiles were obtained from the Gene Expression Omnibus database. Subsequent analyses included differential expression gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) on the combined datasets. We performed functional enrichment analysis on the overlapping genes between DEGs and module genes and constructed a protein-protein interaction network. Using Cytoscape software, we identified hub genes related to the disease and conducted gene set enrichment analysis on these hub genes. The CIBERSORT algorithm was employed to evaluate the correlation between hub genes and the abundance of immune cells within tissues. Finally, Mendelian randomization analysis was utilized to assess the potential of these hub genes as biomarkers. We identified 46 differentially expressed genes (DEGs), comprising 20 upregulated and 26 downregulated genes. Using WGCNA, we constructed a gene co-expression network and selected the most relevant modules, resulting in 24 intersecting genes with the DEGs. KEGG enrichment analysis of the intersecting genes identified the IL-17 signaling pathway, associated with inflammation, as the most significant pathway. Cytoscape software was utilized to rank the candidate genes, with JUN, ATF3, FOSB, NR4A2, and IL6 emerging as the top five based on the Degree algorithm. A nomogram model incorporating these five genes, supported by ROC curve analysis, validated their diagnostic efficacy. Immune infiltration and correlation analysis revealed that macrophages were significantly associated with JUN (p < 0.01), FOSB (p < 0.01), and NR4A2 (p < 0.05). Additionally, T follicular helper cells showed significant associations with ATF3 (p < 0.05), FOSB (p < 0.05), and JUN (p < 0.05). Mendelian randomization analysis provided strong evidence linking JUN (IVW: OR = 0.910, p = 0.005) and IL6 (IVW: OR = 1.024, p = 0.026) with KOA. Through the utilization of various bioinformatics analysis methods, we have pinpointed key hub genes relevant to knee osteoarthritis. These findings hold promise for advancing pre-symptomatic diagnostic strategies and enhancing our understanding of the biological underpinnings behind knee osteoarthritis susceptibility genes.

Modulation of chondroprotective hyaluronic acid and poloxamer gel with Ketoprofen loaded transethosomes: Quality by design-based optimization, characterization, and preclinical investigations in osteoarthritis

Osteoarthritis (OA) is a chronic joint disease that results in biomechanical and morphological changes that contribute to cartilage degradation. Ketoprofen (KP), used in the treatment of OA, is a selective inhibitor of cyclooxygenase-2 (COX-2). Topical administration of KP bypasses gastric irritation as well as first-pass metabolism and increases localized delivery. The research intricates fabrication and optimization of KP-loaded transethosomes (KP-TEs) via Taguchi orthogonal array design and Central composite design (CCD). The optimized KP-TEs depicted an average vesicle size of 110.0 ± 1.70 nm, poly dispersibility index (PDI) of 0.103 ± 0.01, zeta potential −6.08 ± 0.27 mV, and conductivity of 0.049 ± 0.0001 mS/cm. The optimized KP-TEs were loaded in composite hyaluronic acid (HA) and poloxamer 407 (Px407) for an improvement of osteotrophic and chondroprotective transethosomal gel. The drug content of KP-TEs-HA/Px407 gel was found to be 90.08 ± 1.25 %. Preclinical research has been carried out by using the monosodium iodoacetate to develop model for osteoarthritis in male wistar rats. The X-ray imaging of KP-TEs-HA/Px407 gel treated group showed intact meniscus, healthy articular joint, and normal synovial lining same as the healthy control group. The IL − 1β IL-6, IL-22, TNF-α, and IL-10, levels, X-ray imaging, and studies on histopathology demonstrated the effectiveness of transethosomal gel in reducing pain and inflammation.

Regulatory effect and mechanism of CircSEC24A in IL-1β-induced osteoarthritis

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment.

A Novel Curcumin-Loaded Nanoplatform Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin-loaded nanoparticles (Cur-NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe2⁺), and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron-chelating properties. The in vitro anti-ferroptotic effects of Cur-NPs are thoroughly investigated. The findings indicate that Cur-NPs decrease the expression of ferroptosis markers such as ROS, Fe2⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur-NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur-NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur-NPs exhibit enhanced chondroprotective effects through anti-ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.

Aptamer-Modified Tetrahedral Framework Nucleic Acid Synergized with TGF-β3 to Promote Cartilage Protection in Osteoarthritis by Enhancing Chondrogenic Differentiation of MSCs.

Characterized by progressive and irreversible degeneration of the articular cartilage (AC), osteoarthritis (OA) is the most common chronic joint disease, and there is no cure for OA at present. Recent studies suggest that enhancing the recruitment of endogenous mesenchymal stem cells (MSCs) to damaged cartilage is a promising therapeutic strategy for cartilage repair. Tetrahedral framework nucleic acid (tFNA) is a novel DNA nanomaterial and has shown great potential in the field of biomedical science. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, is considered to induce chondrogenesis. A 66-base DNA aptamer named HM69 is reported to identify and recruit MSCs. In this study, aptamer HM69-modified tFNAs were successfully self-assembled and used to load TGF-β3 when the disulfide bonds combined. We confirmed the successful synthesis of the final composition, HM69-tFNA@TGF-β3 (HTT), by PAGE, dynamic light scattering, and atomic force microscopy. The results of in vitro experiments showed that HTT effectively induced MSC proliferation, migration, and chondrogenic differentiation. In addition, HTT-treated MSCs were shown to protect the OA chondrocytes. In DMM mice, the injection of HTT improved the therapeutic outcome of mouse pain symptoms and AC degeneration. In conclusion, this study innovatively used the disulfide bonds combined with TGF-β3 and tFNA, and an additional sequence HM69 was loaded on tFNA for the better-targeted recruitment of MSCs. HTT demonstrated its role in promoting the chondrogenesis of MSCs and cartilage protection, indicating that it might be promising for OA therapy.

A bibliometric analysis of the application of physical therapy in knee osteoarthritis from 2013 to 2022.

Knee osteoarthritis (KOA) is one of the most common chronic joint diseases. Physical therapy, a non-invasive approach, is extensively used in its treatment. Although bibliometrics is a reliable method to evaluate the significance and impact of research fields, systematic bibliometric analyses in this area are lacking. This study aims to perform a bibliometric analysis covering 2013 to 2022, to highlight the current state, key focuses, and trends in physical therapy for KOA. This study utilizes the Web of Science Core Collection to gather relevant literature on physical therapy and KOA from 2013 to 2022. CiteSpace and VOSviewer software facilitated the visual analysis of the annual publications, geographic and institutional distributions, journals, authors, references, and keywords in this field. The study analyzed 1,357 articles, showing an overall increase in publications over time from 71 countries and 2,302 institutions. The United States and Australia emerged as leaders in this field. The analysis identified 6,046 authors, with Kim L. Bennell as the most prolific and Bellamy N. receiving the most citations. BMC Musculoskeletal Disorders published the most articles, while Osteoarthritis and Cartilage received the most citations. High-impact articles were authored notably by McAlindon TE, Bannuru RR, Fernandes L, and Bennell KL. Keyword analysis highlighted a strong focus on patient self-management, exercise therapy, physical factor therapy, and remote rehabilitation. The bibliometric analysis confirms significant interest and ongoing research in physical therapy for KOA treatment from 2013 to 2022, indicating a growing field. Journals and authors in this area show influential and collaborative dynamics. Future research should focus on enhancing international and institutional collaboration and explore emerging trends like internet-guided treatments.

The Multifaceted Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 in Osteoarthritis: Regulation of Oxidative Stress and Inflammation.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease's progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2's impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2's role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2's protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA.

New insights into the mechanisms and therapeutic strategies of chondrocyte autophagy in osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease with an unclear cause characterized by secondary osteophytes and degenerative changes in the articular cartilage. More than 250 million people are expected to be affected by it by 2050, putting a tremendous socioeconomic strain on the entire world. OA cannot currently be treated with any effective medications that change the illness. Over time, chondrocytes undergo gradual metabolic, structural, and functional changes as a result of aging or abuse. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte homeostasis. By continuously recycling and rebuilding macromolecules or organelles, autophagy functions as a crucial regulatory system to maintain homeostasis during an individual's growth and development. This review uses chondrocytes as its starting point and establishes a strong connection between autophagy and osteoarthritis in order to thoroughly examine the mechanisms behind chondrocyte autophagy in osteoarthritis. Biomarkers of chondrocyte autophagy will be identified, and prospective targeted medications and novel treatment approaches for slowing or preventing the course of OA will be developed based on chondrocyte senescence, autophagy, and apoptosis in OA. KEY MESSAGES: Currently, OA has not been treated with any drugs that can effectively cure it. We hope that by exploring specific targets in the course of osteoarthritis, we can promote the progress of treatment strategies. The degenerative progression of osteoarthritis is significantly influenced by the imbalance of chondrocyte balance. Through the continuous recovery and reconstruction of macromolecules or organelles, autophagy is an important regulatory system for maintaining homeostasis during individual growth and development. In this paper, the close relationship between autophagy and osteoarthritis was established with chondrocytes as the starting point, in order to further explore the mechanism of chondrocyte autophagy in osteoarthritis. The development process of osteoarthritis was studied from the perspective of chondrocytes, and the change of autophagy level had a significant impact on osteoarthritis. Chondrocyte autophagy is mainly determined by intracellular mitochondrial autophagy, so we are committed to finding relevant molecules. Through PI3K/AKT- and MAPK-related pathways, the biomarkers of chondrocyte autophagy were identified, and chondrocyte senescence, autophagy, and apoptosis based on osteoarthritis provided a constructive idea for the development of prospective targeted drugs and new therapies to slow down or prevent the progression of osteoarthritis.

Gubi decoction mitigates knee osteoarthritis via promoting chondrocyte autophagy through METTL3-mediated ATG7 m6A methylation.

Knee osteoarthritis (KOA) is a chronic joint disease that significantly affects the health of the elderly. As an herbal remedy, Gubi decoction (GBD) has been traditionally used for the treatment of osteoarthritis-related syndromes. However, the anti-KOA efficacy and mechanism of GBD remain unclear. This study aimed to experimentally investigate the anti-KOA efficacy and the underlying mechanism of GBD. The medial meniscus (DMM) mice model and IL-1β-stimulated chondrocytes were, respectively, constructed as invivo and invitro models of KOA to evaluate the osteoprotective effect and molecular mechanism of GBD. The UPLC-MS/MS analysis showed that GBD mainly contained pinoresinol diglucoside, rehmannioside D, hesperidin, liquiritin, baohuoside I, glycyrrhizic acid, kaempferol and tangeretin. Animal experiment showed that GBD could alleviate articular cartilage destruction and recover histopathological alterations in DMM mice. In addition, GBD inhibited chondrocyte apoptosis and restored DMM-induced dysregulated autophagy evidenced by the upregulation of ATG7 and LC3 II/LC3 I but decreased P62 level. Mechanistically, METTL3-mediated m6A modification decreased the expression of ATG7 in DMM mice, as it could be significantly attenuated by GBD. METTL3 overexpression significantly counteracted the protective effect of GBD on chondrocyte autophagy. Further research showed that GBD promoted proteasome-mediated ubiquitination degradation of METLL3. Our findings suggest that GBD could act as a protective agent against KOA. The protective effect of GBD may result from its promotion on chondrocyte autophagy by suppressing METTL3-dependent ATG7 m6A methylation.

Composition, Skin Pharmacokinetics, and Pharmacological Effects of the Sanfu Herbal Patch

The Sanfu herbal patch (SHP) is a traditional Chinese medicine external therapy consisting of Sinapis semen, Asari Radix et Rhizoma, Kansui Radix, and Corydalis Rhizoma. The review involved searching for SHP-related keywords in various databases including Web of Science, PubMed, and China National Knowledge Infrastructure, etc Relevant literature was then selected and findings were summarized. The SHP encompasses a diverse array of bioactive constituents, such as fatty acids, thioglycosides, essential oils, terpenes, alkaloids, and additional chemical compounds. The parent constituents of the SHP that enter skin circulation mainly include sinapine thiocyanate from Sinapis semen, asarinin from Asari Radix et Rhizoma, and tetrahydropalmatine from Corydalis Rhizoma. The SHP exhibits anti-inflammatory, antitussive, analgesic, and antitumor properties, making it a valuable pharmacological agent. Moreover, the SHP is frequently employed in clinical settings to address various ailments including asthma, rhinitis, chronic bronchitis, chronic obstructive pulmonary disease, chronic degenerative joint disease, and chronic gastritis. This review focuses on the main components, skin pharmacokinetics, and pharmacological research progress of the SHP, offering valuable insights for further understanding its mechanism of action and enhancing its clinical application.

Identification and verification of four candidate biomarkers for early diagnosis of osteoarthritis by machine learning

BackgroundOsteoarthritis (OA) is a common chronic joint disease. This study aimed to investigate possible OA diagnostic biomarkers and to verify their significance in clinical samples. MethodsWe exploited three datasets from the Gene Expression Omnibus (GEO) database, serving as the training set. We first determined differentially expressed genes and screened candidate diagnostic biomarkers by applying three machine learning algorithms (Random Forest, Least Absolute Shrinkage and Selection Operator logistic regression, Support Vector Machine-Recursive Feature Elimination). Another GEO dataset was used as the validation set. The test set consisted of RNA-sequenced peripheral blood samples collected from patients and healthy donors. Blood samples and chondrocytes were collected for quantitative real-time PCR to confirm expression levels. Receiver operating characteristic curves were generated for individual and combined biomarkers. ResultsIn total, 251 DEGs were screened, where B3GALNT1, SCRG1 and ZNF423 were screened by all three algorithms. The area under the curve (AUC) of various biomarkers in our test set did not reach as high as that in public datasets. GRB10 exhibited highest AUC of 0.947 in the training set but 0.691 in our test set, while the favorable combined model comprising B3GALNT1, GRB10, KLF9 and SCRG1 demonstrated an AUC of 0.986 in the training set, 1.000 in the validation set and 0.836 in our test set. ConclusionWe identified a combined model for early diagnosis of OA that includes B3GALNT1, GRB10, KLF9 and SCRG1. This finding offers new avenues for further exploration of mechanisms underlying OA.

Britanin alleviates chondrocyte ferroptosis in osteoarthritis by regulating the Nrf2-GPX4 axis

BackgroundOsteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage or inflamed joints. Britanin is a guaiacyl-type sesquiterpene lactone possessing anti-inflammatory and antioxidant activities. MethodsIn this study, western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescent staining method were used to clarifying the molecular mechanisms of britanin in alleviating chondrocyte ferroptosis. The effect of britanin on reactive oxygen species (ROS) and lipid peroxidation levels in chondrocytes was examined by Dihydroethidium (DHE) stain and fluorescent dye BODIPY581 / 591 C11. The destabilized medial meniscus (DMM) model was used to mimic OA, then britanin was injected into the knee articular cavity. The morphological analysis was performed by hematoxylin and eosin (H&E) staining, Safranin O-Fast green staining and Micro-computed tomography (Micro-CT) analysis. Immunohistochemical analysis and Immunofluorescence assay was conducted to verify the effect of britanin in vivo. ResultsThe results revealed that britanin treatment regulates the expression of chondrocyte extracellular matrix–related factors, such as ADAMTS5, MMP13, SOX9, aggrecan, and COL2A1. Britanin also significantly reversed the influence of interleukin (IL)-1β on the levels of reactive oxygen species and lipid peroxidation and upregulated glutathione peroxidase 4 (GPX4) expression in IL-1β-induced chondrocytes. Erastin could alleviate the effects of britanin on chondrocytes. Moreover, britanin could prevent IL-1β-induced oxidative stress and ferroptosis in chondrocytes. Britanin also upregulated the expression of nuclear factor E2–related factor 2 (Nrf2) in IL-1β-induced chondrocytes, and Nrf2 activator played a similar role as that of britanin in IL-1β-induced chondrocytes. Furthermore, injecting britanin into the knee joints of OA rats alleviated cartilage destruction caused by surgical resection. ConclusionsThese findings confirmed that britanin can inhibit ferroptosis in OA chondrocytes through the Nrf2-GPX4 pathway. Thus, britanin has the potential to be developed as a drug for OA therapy.

Recent Advances in Hydrogel Technology in Delivering Mesenchymal Stem Cell for Osteoarthritis Therapy.

Osteoarthritis (OA), a chronic joint disease affecting over 500 million individuals globally, is characterized by the destruction of articular cartilage and joint inflammation. Conventional treatments are insufficient for repairing damaged joint tissue, necessitating novel therapeutic approaches. Mesenchymal stem cells (MSCs), with their potential for differentiation and self-renewal, hold great promise as a treatment for OA. However, challenges such as MSC viability and apoptosis in the ischemic joint environment hinder their therapeutic effectiveness. Hydrogels with biocompatibility and degradability offer a three-dimensional scaffold that support cell viability and differentiation, making them ideal for MSC delivery in OA treatment. This review discusses the pathological features of OA, the properties of MSCs, the challenges associated with MSC therapy, and methods for hydrogel preparation and functionalization. Furthermore, it highlights the advantages of hydrogel-based MSC delivery systems while providing insights into future research directions and the clinical potential of this approach.