Animal Models Of Osteoarthritis Research Articles

Recent Trends in Adipose Tissue-Derived Injectable Therapies for Osteoarthritis: A Scoping Review of Animal Models

Background and Objectives: This scoping review investigates recent trends in adipose tissue-derived injectable therapies for osteoarthritis (OA) in animal models, focusing on minimally manipulated or lightly processed adipose tissue. By evaluating and examining the specific context in which these therapies were investigated across diverse animal OA models, this review aims to provide valuable insights that will inform and guide future research and clinical applications in the ongoing pursuit of effective treatments for osteoarthritis. Materials and Methods: This research conducted a comprehensive literature review of PubMed and Embase to determine studies about minimally manipulated adipose tissue-derived injectable therapies for osteoarthritis investigated using animal models. The primary search found 530 results. After excluding articles that focused on spontaneous osteoarthritis; on transfected, preconditioned, cultured, or co-cultured adipose-derived stem cells; and articles with unavailable full text, we included 11 articles in our review. Results: The examined therapies encompassed mechanical micro-fragmented adipose tissue (MFAT) and stromal vascular fraction (SVF) obtained via collagenase digestion and centrifugation. These interventions were evaluated across various animal models, including mice, rats, rabbits, and sheep with induced OA. Notably, more studies concentrated on surgically induced OA rather than chemically induced OA. The assessment of these therapies focused on elucidating their protective immunomodulatory, anti-inflammatory, and chondroregenerative potential through comprehensive evaluations, including macroscopic assessments, histological analyses, immunohistochemical examinations, and biochemical assays. Conclusions: This review provides a comprehensive analysis of adipose tissue-derived injectable therapies for osteoarthritis across diverse animal models. While revealing potential benefits and insights, the heterogeneity of data and the limited number of studies highlight the need for further research to formulate conclusive recommendations for clinical applications.

Eficacia de nuevos viscosuplementos activos en el comportamiento de un modelo experimental de osteoartritis

Objective: to evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs.Material and methods: experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II to V, the infiltration of the corresponding compound was carried out spaced one week apart.Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis.Results: We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed.The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III).Conclusions: The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

Progress in the Establishment of Animal Models of Osteoarthritis

Progress in the Establishment of Animal Models of Osteoarthritis

Reproducible Synthesis of Biocompatible Albumin Nanoparticles Designed for Intra-articular Administration of Celecoxib to Treat Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage. As pharmaceutical utility also demands that this is achieved using biocompatible materials that provide colloidal stability, our aim was to develop a nanoparticle (NP) delivery system loaded with the COX-2 inhibitor celecoxib that can meet these criteria. We devised a reproducible and economical method to synthesize the colloidally stable albumin NPs loaded with celecoxib without the use of any of the following conditions: high temperatures at which albumin denaturation occurs, polymer coatings, oils, Class 1/2 solvents, and chemical protein cross-linkers. The spherical NP suspensions were biocompatible, monodisperse with average diameters of 72 nm (ideal for OA cartilage penetration), and they were stable over 6 months at 4 °C. Moreover, the NPs loaded celecoxib at higher levels than those required for the therapeutic response in arthritic joints. For these reasons, they are the first of their kind. Labeled NPs were internalized by primary human articular chondrocytes cultured from the knee joints of OA patients. The NPs reduced the concentration of inflammatory mediator prostaglandin E2 released by the primaries, an indication of retained bioactivity following NP synthesis. Similar results were observed in lipopolysaccharide-stimulated human THP-1 monocytes. The IA administration of these NPs is expected to avoid side-effects associated with oral administration of celecoxib and to maintain a high local concentration in the knee joint over a sustained period. They are now ready for evaluation by IA administration in animal models of OA.

Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats.

Osteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

Do we understand sex-related differences governing dimorphic disease mechanisms in preclinical animal models of osteoarthritis?

Research conducted using murine preclinical models of osteoarthritis (OA) over the last three decades has brought forth many exciting developments showcasing mechanisms and pathways that ‎drive disease pathogenesis. These models have identified therapeutic targets that can be modulated via innovative biologicals and pharmaceuticals. However, many of these ‎approaches have failed to translate to humans and reach the clinic. This commentary aims to highlight some of the key ‎hurdles in the translation of novel findings using preclinical OA models. While the focus of this commentary is on OA-related joint structural aberrations dictated by chondrosenescence, other signaling mechanisms have been shown to be affected by sexual dimorphism (i.e TGFβ signalling, EGFR/integrin α1β1 and Trpv4). Preclinical models of OA mainly utilize male mice ‎due to their capacity to capitulate a fast progressing OA structural phenotype compared to ‎female mice. This experimental trend has overlooked and ignored the sex-related effects of numerous mechanisms affecting joint structure, that ‎influence OA structural progression. Future work should focus on analysing both sexes ‎and understanding sex-related differences, which will enable ‎us to gain a better understanding of the progression of OA based on sex-related mechanistic discrepancies.

Green synthesis of gold nanoparticles mediated by extract of Curcuma longa under ultrasonic condition: Investigation of its application for reduction of dye pollutants and repairing the articular cartilage in an animal model of osteoarthritis of the knee

For environmental remediation, it is crucial to find effective heterogeneous catalysts that can remove organic contaminants or convert them into chemicals that are safe and even valuable. Here, we present the synthesis of a green gold-based catalyst using an extract of Curcuma longa (Au NPs@C. longa) under ultrasonic condition. This nanocatalyst demonstrated good performance for reduction of organic dyes including methyl orange, methylene blue, and 4-nitrophenol. FE-SEM in conjunction with EDS, TEM, and UV–visible spectroscopy were used to evaluate the produced nanocatalyst. The Au NPs@C. longa should show great promise for wastewater treatment since it has the advantages of good activity, good kinetics and suitable stability for dye reduction. In the orthopedic experiments, the efficacy of Au NPs@C. longa on chondrogenesis was assessed by the primary cultured chondrocytes. Western blot, PCR, and histological assays were done to follow the underlying mechanisms. We evaluated the functional recovery after Au NPs@C. longa transplantation by an osteoarthritis articular cartilage injury model in knee. In immunological section, the Au NPs@C. longa reduced the levels of TNF-α, IL-1β, MMPs, and p-p65 expression. This may be caused by adjusting cellular redox homeostasis related to the Nrf2. The data indicated the positive efficacy of Au NPs@C. longa on stimulating chondrogenesisin vitro. It was revealed that the Au NPs@C. longa application speeded up the injury-induced dysfunction recovery after 21 days. The Au NPs@C. longa application suppressed the abnormal fibrosis and angiogenesis at the injury site.

Analysis of joint protein expression profile in anterior disc displacement of TMJ with or without OA.

Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the invitro and invivo results are consistent with protein changes detected in MS profile. This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets.

In Vivo Detection of Staphylococcus aureus Infections Using Radiolabeled Antibodies Specific for Bacterial Toxins.

The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α-toxin released by S. aureus. [89Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti-α-toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus) and infective osteoarthritis. Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus. Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [89Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes. We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [89Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes.

A comparative study of oral diacerein and transdermal diacerein as Novasomal gel in a model of MIA induced Osteoarthritis in rats

Background: Osteoarthritis is a chronic pathology of the joints causing disability and morbidity. Diacerein is a disease-modifying agent indicated for osteoarthritis management with enhanced performance and have much lower side effects profile than conventional non-steroidal anti-inflammatory drugs. Oral administration of Diacerein is associated with a laxative effect , thus causing treatment discontinuation. Aim: This study aimed to evaluate the activity of Diacerein novasome-based transdermal gel compared with standard oral treatment in the management of induced osteoarthritis in a rat model. Materials and methods: A single intra-articular injection of monosodium iodoacetate was administered to the left knee joint, resulting in the development of Osteoarthritis. Disease progression and the effect of both routes of Diacerein treatment were evaluated by morphological, biochemical, histological, and radiological studies. Results: Osteoarthritis was successfully induced in rats’ knee joints. Morphological studies revealed that both Diacerein treatments significantly reduced joint swelling as compared to the untreated group. The serum TNF-α and IL-1β levels were significantly lower in both Diacerein treatment groups as compared to the untreated group throughout the course of the study. Histological and radiological findings confirmed that transdermal Diacerein treatment protects against cartilage degradation like oral treatment. Conclusion: Novasomal technology proved its efficacy as a carrier for the transdermal delivery of Diacerein. The in-vivo study on an animal model of osteoarthritis showed that Diacerein transdermal gels provided sufficient pharmacological activity for the attenuation of the disease. This finding could support its use as an alternative to the standard oral treatment to avoid side effects.

The Immunological Facets Of Chondrocytes In Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a disease in which the pathogenesis affects the joint and its surrounding tissues. Cartilage degeneration is the main hallmark of OA and chondrocytes within the cartilage regulate matrix production and degradation. In OA patients and animal models of OA, the pathology of the disease relates to disequilibrium between anabolic and catabolic states of the cartilage. Moreover, chondrocyte phenotype and function are also immunologically altered. Under inflammatory conditions, chondrocytes increase production levels of inflammatory cytokines and cartilage-degrading enzymes, which further drive cartilage destruction. Chondrocytes also have an innate immune function and respond to DAMPs and cartilage fragments via innate immune receptors. In addition, chondrocytes play a role in adaptive immune responses by acting as antigen presenting cells and presenting cartilaginous antigens to T cells. Indirectly, chondrocytes are stimulated by pathogen-associated molecular patterns (PAMPs) present in the joints, a result of the microbiota in the host. Chondrocytes have both direct and indirect relationships with immune cells and the immune compartment of OA patients. Therefore, chondrocytes serve as a target for immunotherapeutic approaches in OA. In this narrative review, we cover the aforementioned immune-related aspects of chondrocytes in OA.

Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis

The involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell death in the progression of osteoarthritic cartilage degradation. An in vivo medial meniscus destabilization (DMM)-induced OA animal model as well as an in vitro examination of chondrocytes in an OA microenvironment induced by interleukin-1β (IL-1β) exposure were employed. Histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability, and Micro-CT analysis were utilized in conjunction with gene overexpression and knockdown to evaluate the chondroprotective effects of Sar in OA progression and the role of Yes-associated protein 1 (YAP1) in Sar-induced ferroptosis resistance of chondrocytes. In this study we found Sar reduced chondrocyte ferroptosis and OA progression. And Sar-induced chondrocyte ferroptosis resistance was mediated by YAP1. Furthermore, infection of siRNA specific to YAP1 in chondrocytes reduced Sar's chondroprotective and ferroptosis-suppressing effects during OA development. The findings suggest that Sar mitigates the progression of osteoarthritis by decreasing the sensitivity of chondrocytes to ferroptosis through the promotion of YAP1, indicating that Sar has the potential to serve as a therapeutic approach for diseases associated with ferroptosis.

Development of Anti-OSCAR Antibodies for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

New approach to testing treatments for osteoarthritis: FastOA

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure...

Activities of sondhep herbs to cause changes in IL-1β in an osteoarthritis rat model

Background: Osteoarthritis (OA) is a slowly progressive and degenerative joint disease. Symptoms of pain and inflammation are influenced by IL-1β, which increases COX-2 enzyme activity and PGE2 production. Sumenep Sondhep herbs are used by the community for joint pain.      Objective: To evaluate the activities of the Sumenep Sondhep herb in reducing the cytokine IL-1β in the OA rats model. Methods: Monosodium iodoacetate (MIA) induction was carried out on animal OA models. Rats were treated with Sondhep extract for 28 days. Knee diameter and hyperalgesia responses were recorded every week until the 7th week. The IL-1β levels were observed on the 21st and 49th days using the ELISA method.      Results: There was a significant difference in decreasing the diameter of the rat's knee (p &lt; 0.05), increasing the hyperalgesia test in the rats (p &lt; 0.05), and decreasing IL-1β levels between before and after treatment (p &lt; 0.05).        Conclusion: The Sondhep Sumenep herb has activity against osteoarthritis by reducing pro-inflammatory cytokine IL-1β in OA rat models.

MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCsSC-Exos), especially engineering MSCsSC-Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCsSC-Exos on cartilage repair and therapy of engineering MSCsSC-Exos for drug delivery in OA. MSCsSC-Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCsSC-Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCsSC-Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCsSC-Exos on injured cartilage, engineering exosomes derived from MSCsSC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCsSC-Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCsSC-Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCsSC-Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCsSC-Exos-based strategy for OA therapy and promote the application of targeted-MSCsSC-Exos for drug delivery in the future.Graphical

Description of Novel Molecular Factors in Lumbar DRGs and Spinal Cord Factors Underlying Development of Neuropathic Pain Component in the Animal Model of Osteoarthritis.

Osteoarthritis (OA) is one of the most common joint disorder, with pain accompanied by functional impairment, as the most pronounced clinical symptom. Currently used pharmacotherapy involves symptomatic treatment that do not always provide adequate pain relief. This may be due to concomitance of central sensitization and development of neuropathic features in OA patients. Here we performed studies in the animal model of OA to investigate of the neuropathic component. Intraarticular injection of monoiodoacetate (MIA, 1mg) was used to induce OA in Wistar male rats. Development of pain phenotype was assessed by behavioral testing (PAM test and von Frey's test), while corresponding changes in dorsal root ganglia (DRGs L3-L5) and spinal cord (SC) gene expression were assessed by means of qRT-PCR technique. We also performed microtomography of OA-affected knee joints to correlate the level of bone degradation with observed behavioral and molecular changes. We observed gradually developing remote allodynia after MIA treatment, indicating the presence of neuropathic component. Our results showed that, among DRGs innervating knee joint, development of central sensitization is most likely due to peripheral input of stimuli through DRG L5. In SC, development of secondary hypersensitivity correlated with increased expression of TAC1 and NPY. Our studies provided molecular records on abnormal activation of pain transmission markers in DRG and SC during development of OA that are responsible for the manifestation of neuropathic features. The obtained results increase insight into molecular changes occurring in the neuronal tissue during OA development and may contribute to readdressing treatment paradigms.

A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.

Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts.

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.