Osteoarthritis Therapy Research Articles

Patient needs, functional requirements, aesthetic preferences and barriers in app-based therapy for knee osteoarthritis

Patient needs, functional requirements, aesthetic preferences and barriers in app-based therapy for knee osteoarthritis

Osteoarthritis: An Update on Diagnosis & Management.

Osteoarthritis (OA) is the most prevalent joint condition. It is a progressively degenerating disease that involves the entire joint, including the articular cartilage, subchondral bone, ligaments, capsule, synovial fluid, and periarticular muscles. Physicians understand that osteoarthritis is diagnosed late during the illness, which may be too late for patients to receive significant benefits from medications that change their condition. The goals of OA therapy are to preserve function while minimizing pain and stiffness. This article focuses on the current and potential treatments for osteoarthritis and various diagnostic methodologies for this disease. In the coming years, despite having numerous treatments for symptomatic relief, the treatment plan should be more specialized because everyone might experience improved outcomes.

Lesion-localized hydrogels functionalized with engineered extracellular matrix restore cellular homeostasis by enhancing mitochondrial energy metabolism for osteoarthritis therapy

Cartilage damage and degeneration are fundamental pathological features of osteoarthritis (OA), attributed largely to disruptions in chondrocyte homeostasis. Tissue engineering employing functional bioactive materials presents a promising avenue for cartilage regeneration and repair. Particularly, extracellular matrix (ECM) produced by mesenchymal stem cells (MSCs) is gaining traction in the field of tissue engineering and scaffold-based regenerative therapies due to its robust bioactivity and excellent biocompatibility. In this study, we utilized specific inflammatory cytokines associated with OA as stimulators to optimize the MSC-derived secretome. Our in vitro experiments demonstrated that the engineered ECM effectively inhibited early chondrocyte apoptosis, reversed cellular senescence, and maintained anabolic-catabolic equilibrium. Moreover, we developed aldehyde- and methacrylic anhydride-modified hyaluronic acid hydrogels incorporated with ECM (ECM@AH) using photo-cross-linking techniques. The affinity of these ECM-functionalized hydrogels for degraded cartilage was confirmed through in situ cartilage lesion localization experiments in the knee joints of rat OA models. Further in vitro analysis revealed that the engineered ECM@AH, especially IFN-γ-ECM@AH, sustains chondrocyte homeostasis by restoring mitochondrial energy metabolism. Animal studies demonstrated that ECM@AH, localized to cartilage lesions, could reverse cartilage matrix degradation and promote cartilage repair, underscoring the potential of this biomaterial in OA treatment.

Semi-invasive therapies for pain in knee osteoarthritis: A systematic review and network meta-analysis.

The increasing number of semi-invasive pain therapies in knee osteoarthritis poses challenges in decision-making. This review aimed to simultaneously compare established intra-articular therapies with newer peri-articular therapies and explore effect modifiers. Randomized controlled trials were searched from five electronic databases without date or language restrictions. Study selection and data extraction of reports, retrieved up to May 2024, were performed independently by paired assessors. The primary outcome was 6-month pain score. Nine treatments were included. The effect size (ES) for each treatment, relative to placebo, was estimated using standardized means difference and expressed with 95% confidence intervals (CI). The rigor of results was evaluated with subgroup/sensitivity analyses. A total of 111 studies (14,695 participants) were included, with intra-articular hyaluronic acid having the greatest number of participants. Neuroablation demonstrated the greatest ES (1.08, 95% CI: 0.07, 2.10). While platelet-rich plasma (PRP) ranked second (ES: 0.75, 95% CI: 0.28, 1.22), it was the only intervention demonstrating statistically significant effect at 3, 6, and 12 months. However, this statistical significance was lost in some sensitivity analyses. Larger estimates for biologics and PRP compared with prolotherapy, steroid, and hyaluronic acid injections were consistently observed across different timepoints and in multiple sensitivity analyses. Generally, no statistically significant difference was found between the nine types of therapies. Although there is robust evidence suggesting greater efficacy of PRP, potentially including biologics, over other interventions, future research is needed to identify the phenotype or patient subgroup that would benefit most from PRP.

Interleukin-37 Inhibits Interleukin-1β-Induced Articular Chondrocyte Apoptosis by Suppressing Reactive Oxygen Species.

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of IL-37 in the regulation of cellular apoptosis in rat chondrocytes stimulated by IL-1β. Methods: Rat chondrocytes were used in in vitro study, and were stimulated with IL-1β (10 ng/mL) and/or recombinant IL-37 (rIL-37; 100 ng/mL) after cytotoxicity assessments using these cytokines were conducted. After rIL-37 treatment of chondrocytes stimulated with IL-1β, the cell proliferation assay, apoptosis assays, including expression of mitochondrial apoptosis-related markers, flow cytometry analysis of annexin V-FITC/propidium iodide (PI), cell cycle analysis, and Hoechst 33342 staining, and reactive oxygen species (ROS) measurement were used. Results: IL-1β induced expression of inflammatory cytokines and triggered degradation of the extracellular matrix of rat chondrocytes, but this effect was significantly attenuated by rIL-37 treatment. Enhanced ROS generation following IL-1β stimulation was reduced in a dose-dependent manner after stimulation with rIL-37. IL-1β induced pro-apoptotic markers and suppressed anti-apoptotic markers in rat chondrocytes. Flow cytometry using annexin V-FITC/PI revealed that IL-1β increased the apoptosis rate of rat chondrocytes, and that this effect was markedly reversed by treatment with rIL-37. Conclusions: IL-37 potently attenuated IL-1β-mediated apoptosis of rat chondrocytes by blocking ROS production. This study suggests that IL-37 can serve as a novel anti-cytokine therapy in OA by blocking chondrocyte apoptosis.

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.

Kongensin A targeting PI3K attenuates inflammation-induced osteoarthritis by modulating macrophage polarization and alleviating inflammatory signaling

The inflammatory microenvironment, polarization of macrophages towards the M1 phenotype, and consequent matrix degradation and senescence of chondrocytes are primary contributors to the degeneration of knee joint cartilage, further exacerbating the progression of osteoarthritis (OA). Kongensin A (KA) is a recently identified natural plant extract exhibiting anti-necrotic apoptosis and anti-inflammatory properties, but the potential efficacy in alleviating OA remains uncertain. The current research lucubrated the effect of KA on the inflammatory microenvironment and macrophage polarization, as well as its regulatory function in extracellular matrix (ECM) metabolism and chondrocyte senescence. Our findings demonstrated that KA can suppress inflammatory signaling, maintain homeostasis between ECM anabolism and catabolism, and suppress chondrocytes senescence. Further investigation elucidated that the mechanism involves the suppression of the PI3K/AKT/NF-κB axis in chondrocytes under inflammatory conditions. Moreover, KA impeded M1 polarization of macrophages via inhibiting PI3K/AKT/NF-κB axis. Subsequently, we treated chondrocytes with macrophages-derived conditioned medium (CM) and revealed that KA can promote ECM anabolism and alleviate chondrocytes senescence by reprogramming macrophage polarization. Consistent with in vitro experiments, in vivo administration of KA demonstrated alleviated cartilage degeneration and delayed progression of OA. Collectively, through obstructing the PI3K/AKT/NF-κB axis, KA can reprogram macrophage polarization, promote matrix metabolism equilibrium, and alleviate chondrocytes senescence, thereby attenuating the pathology of OA. In conclusion, KA may emerge as a promising therapy for OA.

Microneedle-Delivered PDA@Exo for Multifaceted Osteoarthritis Treatment via PI3K-Akt-mTOR Pathway.

Osteoarthritis (OA) is marked by cartilage deterioration, subchondral bone changes, and an inflammatory microenvironment. The study introduces the Microneedle-Delivered Polydopamine-Exosome (PDA@Exo MN), a therapeutic that not only preserves cartilage and promotes bone regeneration but also improves localized drug delivery through enhanced penetration capabilities. PDA@Exo MN shows strong reactive oxygen species(ROS) scavenging abilities and high biocompatibility, fostering osteogenesis and balancing anabolic and catabolic processes in cartilage. It directs macrophage polarization from M0 to the anti-inflammatory M2 phenotype. RNA sequencing of treated chondrocytes demonstrates restored cellular function and activated antioxidant responses, with modulated inflammatory pathways. The PI3K-AKT-mTOR pathway's activation, essential for PDA@Exo's effects, is confirmed via bioinformatics and Western blot. In vivo assessments robustly validate that PDA@Exo MN prevents cartilage degradation and OA progression, supported by histological assessments and micro-CT analysis, highlighting its disease-modifying impact. The excellent biocompatibility of PDA@Exo MN, verified through histological (H&E) and blood tests showing no organ damage, underscores its safety and efficacy for OA therapy, making it a novel and multifunctional nanomedical approach in orthopedics, characterized by organ-friendliness and biosecurity.

Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1–34, PTH 1–34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care.

A tetrahedral framework nucleic acids-based gene therapeutic nanococktail alleviates cartilage damage and protects against osteoarthritis progression

Gene therapy based on therapeutic microRNAs (miRNAs) shows great potential in Osteoarthritis (OA) treatment. However, individual miRNAs application is limited by the single target, the instability, and the low efficiency of cell internalization. Here, we identified two potential candidate miRNAs, miR-140-5p and miR-455-3p, exhibited combined enhancing effects against OA progression. Furthermore, a nanococktail therapeutic platform, T-(140 + 455) was constructed by employing tetrahedral framework nucleic acids (tFNAs) to codeliver miR-140-5p/miR-455-3p and achieve enhanced gene therapy for OA. Compared with the delivery of individual miRNAs, T-(140 + 455) can effectively reverse the cell phenotype and metabolism of OA chondrocytes. Moreover, the nanococktail T-(140 + 455) reprogrammed macrophage polarization by modulating the crosstalk between chondrocytes and macrophages, combatting the damage caused by inflammation. The OA rat model treated with nanococktail T-(140 + 455) exhibited favorable performance in halting cartilage damage and regulating extracellular matrix (ECM) metabolic homeostasis. Thus, tFNA-based nanococktails enhance the delivery and efficacy of miRNAs, offering a promising strategy for OA gene therapy.

Efficacy of non-pharmacological treatments for knee osteoarthritis: A systematic review and network meta-analysis

PurposeThis study aims to conduct a network meta-analysis to compare the clinical efficacy of seven distinct non-pharmacological therapies for knee osteoarthritis. We hope that our research findings can provide reference for clinical practitioners in formulating treatment plans. MethodsThrough a computer-based search, we systematically retrieved randomized controlled trials (RCTs) on non-pharmacological therapies for knee osteoarthritis from eight databases, including CNKI, Wanfang, VIP, PubMed, Web of Science, Embase, Scopus, and The Cochrane Library. Following screening, data extraction, and methodological quality assessment, relevant data were included and analyzed using R 4.2.3 software. ResultsA comprehensive analysis of 24 RCTs involving 2582 patients encompassed seven diverse non-pharmacological therapies. The efficacy rankings, based on Visual Analog Scale (VAS) scores, were as follows: shock wave therapy > needle-knife > laser therapy > acupuncture > ultrasound > exercise > transcutaneous electrical nerve stimulation. Similarly, based on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores, the efficacy rankings were as follows: shock wave therapy > needle-knife > laser therapy > acupuncture > ultrasound > transcutaneous electrical nerve stimulation > exercise. Among the three WOMAC subscales, the efficacy rankings for non-pharmacological therapies were as follows: For stiffness: laser therapy > exercise > shock wave therapy > acupuncture > needle-knife > ultrasound > transcutaneous electrical nerve stimulation; For daily activities: shock wave therapy > laser therapy > needle-knife > acupuncture > ultrasound > transcutaneous electrical nerve stimulation > exercise; For pain: shock wave therapy > needle-knife > laser therapy > acupuncture > exercise > transcutaneous electrical nerve stimulation > ultrasound. ConclusionBased on the currently limited research, we can prioritize the use of shockwave therapy to treat patients with knee osteoarthritis. However, it is essential to emphasize that further rigorous and well-designed randomized controlled trials are necessary to validate the conclusions drawn from this study.

Enhanced drug loading efficiency of polymer nano fluorescent carrier system for osteoarthritis treatment

Osteoarthritis (OA) is a prevalent degenerative joint disease in the elderly, characterized by chondrocyte death and cartilage matrix degradation, influenced by mechanical, biological, and environmental factors. Current treatments focus on surgery, but there is a critical need for effective drug development to advance OA management. In this study, we developed a novel composite material, ALG-BA-8-HQ, composed of alginate (ALG), benzoic acid (BA), and 8-hydroxyquinoline (8-HQ), and subsequently loaded it with compound 1, forming ALG-BA-8-HQ@1. Comprehensive characterization using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Ultraviolet–Visible Spectroscopy (UV–Vis), and fluorescence spectroscopy confirmed the chemical bonding between ALG, BA, and 8-HQ, revealed the surface morphology and microstructure, and demonstrated excellent fluorescence properties. The application of ALG-BA-8-HQ@1 in OA treatment showed promising results, enhancing chondrocyte proliferation and increasing the anti-inflammatory capacity of chondrocytes, indicating its potential for effective OA therapy.

Oxygen vacancy-engineered cerium oxide mediated by copper-platinum exhibit enhanced SOD/CAT-mimicking activities to regulate the microenvironment for osteoarthritis therapy

Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an “oxidation switch” to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases.Graphical

Current Non-Surgical Curative Regenerative Therapies for Knee Osteoarthritis.

Osteoarthritis (OA) is a prevalent musculoskeletal disease affecting middle-aged and elderly individuals, with knee pain as a common complaint. Standard therapy approaches generally attempt to alleviate pain and inflammation, using various pharmacological and non-pharmacological options. However, the efficacy of these therapies in long-term tissue repair remains debated. As an alternative, regenerative medicine offers a promising strategy, with decreased adverse event rates and increasing evidence of safety and efficacy. This review will outline current advances in regenerative medicine for knee OA, emphasizing outpatient clinic-based therapies that use orthobiological and non-biological products. Different strategies based on orthobiologics are discussed as potential regenerative options for the management of knee OA. Cell-free therapies including platelet-rich plasma, autologous anti-inflammatories, exosomes, human placenta extract, and mitochondrial transplantation are discussed, focusing on their potential for cartilage regeneration. Additionally, cell-based therapies with regenerative properties including bone marrow aspirate concentrate, adipose stromal vascular fraction, microfat, nanofat, stem cell therapy, and genetically modified cells as part of orthobiologics, are being investigated. Also, this study is looking into non-biological approaches such as using gold-induced cytokines, extracorporeal shockwave therapy, and ozone therapy. The mechanisms of action, effectiveness, and clinical applications of each therapy are being explored, providing insights into their role in the management of knee OA.

Hydrogel microspheres for stem cell recruitment and induction of directed differentiation in osteoarthritis therapy

The utilization of stem cell biotechnology for osteoarthritis (OA) treatment is hindered by high operational costs, difficulties in maintaining stem cell viability, and limited efficacy of unguided stem cell differentiation. Magnesium ions (Mg2+), crucial for tissue regeneration and repair, hold significant potential in OA treatment. However, further investigation is required to elucidate the precise mechanisms of Mg2+ in OA treatment. Here, we investigated the optimal concentration of Mg2+ to induce directed differentiation of stem cells and synthesized bioactive hydrogel microspheres (MDGM-Ps) capable of precisely releasing this concentration using microfluidic technology. Synthesized via polymerization of dopamine methacrylamide (DMA) and methacrylated gelatin (GelMA), these microspheres could chelate Mg2+ and incorporate platelet-derived growth factor-BB into the hydrogel matrix for sustained release. In vitro, MDGM-Ps showed excellent biocompatibility and promoted stem cell recruitment. Importantly, Mg2+ released from MDGM-Ps could guide stem cell differentiation through the PI3K-AKT pathway. Moreover, in vivo experiments suggested that MDGM-Ps could maintain the cartilage matrix and mitigate the progression of OA. In summary, MDGM-Ps not only harnessed the advantages of stem cell therapy, but also expanded the therapeutic applications of metal ions, thereby presenting a promising candidate for OA therapy.

Injectable Regenerated Silk Fibroin Micro/Nanosphere with Enhanced Permeability and Stability for Osteoarthritis Therapy.

In the therapy of early-stage osteoarthritis, to accomplish full infiltration of subchondral bone and cartilage, and to target osteoclast and chondrocyte simultaneously remain challenges in biomaterials design. Herein, a novel hierarchical drug delivery system is introduced, with micrometer-scale outer layer spheres composed of regenerated silk fibroin, characterized by connected porous structure through the n-butanol and regenerated silk fibroin combined emulsion route and freezing method. The design effectively resists clearance from the joint cavity, ensuring stable delivery and prolonged residence time within the joint space. Additionally, the system incorporates phenylboronic acid-enriched silk fibroin nanoparticles, stabilized through chemical cross-linking, which encapsulate isoliquiritin derived from Glycyrrhiza uralensis. These nanoparticles facilitate complete penetration of the cartilage extracellular matrix, exhibit pH-responsive behavior, neutralize reactive oxygen species, and enable controlled drug release, thereby enhancing therapeutic efficacy. The in vitro and in vivo experiments both demonstrate that the composite micro/nanospheres not only inhibit osteoclastogenesis with bone loss in subchondral bone and osteophyte formation, but also mitigate chondrocytes apoptosis, reduce oxidative stress associated with cartilage degeneration, and ameliorate neuropathic hyperalgesia, with the underlying mechanisms being elucidated. The study indicates that such an injectable strategy combining organic biomaterials with Chinese medicine holds substantial promise for the treatment of early osteoarthritis.

Intra-articular Therapies for Hand Osteoarthritis: a Systematic Review and Network Meta-analysis

Abstract Objective Intra-articular injection therapy for hand osteoarthritis has inconclusive evidence regarding the effectiveness of different regimens. A systematic review and network meta-analysis of randomized controlled trials (RCTs) was conducted to examine the effectiveness of different injectants. Design The PubMed, Cochrane Library, Embase, ClinicalKey, and Scopus databases were searched for studies from inception to July 15, 2023. RCTs that applied intra-articular injection to hand osteoarthritis patients were included, and the outcomes of pain scores and functional scales were assessed. Results 14 RCTs with 674 patients met the inclusion criteria; 11 RCTs were included in the network meta-analysis. Intra-articular injected platelet-rich plasma (PRP) and dextrose significantly improved pain scores (mean difference [MD] = −4.03, 95% confidence interval [CI] = −6.51 to −1.56 for PRP; MD = −1.06, 95% CI = −2.1 to −0.02 for dextrose) and hand function (standard mean difference [SMD] = −0.93, 95% CI = −1.81 to −0.05 for PRP; SMD = −0.84, 95% CI = −1.58 to −0.09 for dextrose) in the long-term (≥6 months after treatment completion). The ranking probabilities revealed the highest effectiveness of PRP, followed by dextrose. No major adverse effects were reported. Conclusion Intra-articular injected PRP and dextrose can be recommended for treating hand osteoarthritis.

ELIXCYTE®, an Allogenic Adipose-Derived Stem Cell Product, Mitigates Osteoarthritis by Reducing Inflammation and Preventing Cartilage Degradation In Vitro.

Adipose-derived stem cells (ADSCs) comprise a promising therapy for osteoarthritis (OA). The therapeutic potential of ELIXCYTE®, an allogeneic human ADSC (hADSC) product, was demonstrated in a phase I/II OA clinical trial. However, the exact mechanism underlying such effects is not clear. Moreover, studies suggest that interleukin-11 (IL-11) has anti-inflammatory, tissue-regenerative, and immune-regulatory functions. Our aim was to unravel the mechanism associated with the therapeutic effects of ELIXCYTE® on OA and its relationship with IL-11. We cocultured ELIXCYTE® with normal human articular chondrocytes (NHACs) in synovial fluid obtained from individuals with OA (OA-SF) to investigate its effect on chondrocyte matrix synthesis and degradation and inflammation by assessing gene expression and cytokine levels. NHACs exposed to OA-SF exhibited increased MMP13 expression. However, coculturing ELIXCYTE® with chondrocytes in OA-SF reduced MMP13 expression in chondrocytes and downregulated PTGS2 and FGF2 expression in ELIXCYTE®. ELIXCYTE® treatment elevated anti-inflammatory cytokine (IL-1RA, IL-10, and IL-13) levels, and the reduction in MMP13 was positively correlated with IL-11 concentrations in OA-SF. These findings indicate that IL-11 in OA-SF might serve as a predictive biomarker for the ELIXCYTE® treatment response in OA, emphasizing the therapeutic potential of ELIXCYTE® to mitigate OA progression and provide insights into its immunomodulatory effects.

Progress and Challenges of Topical Delivery Technologies Meditated Drug Therapy for Osteoarthritis.

Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.

Screen of FDA-approved drug library identifies Vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest–specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL/PI3K/AKT axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.