Osteoarthritis Therapy Research Articles

Microenvironment-Responsive Hydrogels Comprising Engineering Zeolitic Imidazolate Framework-8-Anchored Parathyroid Hormone-Related Peptide-1 for Osteoarthritis Therapy.

Intra-articular drug injections are effective for osteoarthritis (OA), but challenges such as the complex microenvironment and rapid drug diffusion require frequent injections. Herein, we propose a biofunctional hydrogel-based strategy for prolonged drug delivery and microenvironment remodeling. We propose a strategy to functionalize zeolitic imidazolate framework-8 with tannic acid (TA-ZIF), anchor PTH-related peptide-1 (PTHrP-1) within this framework (TA-ZIF@P1) and incorporate a phenylboronic acid-modified gelatin-based hydrogel (GP hydrogel) drug delivery system (GP@TA-ZIF@P1, GPTP hydrogel) with responsive release properties that respond to the pathological microenvironments of OA. The GPTP hydrogel facilitated controlled, sustained release of PTHrP-1 via dynamic boronic esters, with in vitro and in vivo studies showing continuous release for over 28 days. It not only promotes chondrocyte proliferation but also exhibits significant cytoprotective effects under hyperactive ROS and IL-1β-induced conditions. Notably, transcriptome sequencing confirms that the GPTP hydrogel facilitates both chondrocyte proliferation and chondrogenesis under inflammatory conditions by deactivating Wnt/β-Catenin signaling pathways and enhancing the PI3K/AKT signaling pathway. Additionally, the GPTP hydrogel delays the catabolic metabolism of cartilage explants from mice in inflammatory environments. In a surgical model of mouse OA, we show that the intra-articular injection of GPTP hydrogels reduced periarticular bone remodeling and promoted the production of glycosaminoglycans while offering chondroprotection against cartilage degeneration. To sum up, this pioneering research on PTHrP-1 as a treatment for OA, combined with the GPTP hydrogel system, offers valuable insights and a paradigm for the controlled and sustained release of PTHrP-1, representing a significant advancement in OA treatment strategies.

Promising LOX proteins for cartilage-targeting osteoarthritis therapy.

Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, "LOX" proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role. The lipoxygenase enzyme family is involved in the inflammatory process of OA by inducing the production of several pro-inflammatory leukotrienes. Lectin-like oxidized low-density lipoprotein family are receptors located at the surface of chondrocytes, which interact with their ligand, ox-LDL, activating several catabolic pathways involved in OA pathophysiology. Finally, lysyl oxidase and lysyl oxidase-like are enzymes expressed intracellularly (in chondrocytes' cytoplasm) involved in elastin biosynthesis and collagen cross-linking in cartilage extracellular matrix. EMA and FDA have not yet approved any drug targeting the LOX proteins. In particular, today lysyl oxidase-like 2 is considered as a new promising target for OA modifying therapy. This review clarifies the main roles of different LOX proteins involved in the progression of OA. Potential LOX inhibitoion strategies for drug development in advanced OA therapy, particularly for local intraarticular delivery, were listed and discussed for each target type. This review, therefore, proposes promising strategies for future drug development in OA treatment.

Exploring Patient Perspectives and Experiences in Physical Therapy and Treatment Choices for Knee Osteoarthritis in Saudi Arabia: A Qualitative Study

Background: Knee osteoarthritis is a prevalent condition, particularly among older adults, characterized by chronic pain, reduced mobility, and significant impacts on quality of life. While treatments such as physical therapy and surgery exist, patient perceptions and understanding of these options play a critical role in treatment decisions and outcomes. However, there is limited research exploring how patient insights and opinions shape their choices, particularly concerning physical therapy. This study aimed to explore the patient perspectives and experiences in physical therapy and treatment choices for knee osteoarthritis. Methods: Semi-structured interviews were conducted in Arabic with 33 participants diagnosed with knee osteoarthritis, comprising 18 males and 15 females, with a mean age of 53 years (SD = 5.67). The interviews were based on a pre-prepared schedule developed specifically for this study. Braun and Clarke’s thematic analysis was applied to identify themes capturing participants' experiences and perspectives on treatment options and challenges. Results: Participants reported that knee pain prompted them to seek treatment, with physical therapy being chosen more frequently than surgical interventions. Awareness of physical therapy's benefits varied; some felt well-informed and supported by healthcare providers, while others encountered misinformation and emotional resistance. Family and community support systems were helpful, but a lack of education on management options caused confusion and frustration. Conclusion: To optimize the treatment outcomes of knee osteoarthritis, it is essential to address patients' emotional, psychological, and educational needs. Coupled with the benefits of physical therapy, such as pain relief and improved mobility, this holistic approach can enhance treatment adherence and significantly improve patients’ quality of life. Healthcare providers should prioritize patient education, emotional support, and tailored interventions to ensure a comprehensive and patient-centered care experience.

Gut Microbiota and Osteoarthritis: From Pathogenesis to Novel Therapeutic Opportunities.

Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal bone loss, and osteophyte development. Clinical manifestations include inflammatory joint pain, swelling, osteophytes, and limitation of motion. The pathogenesis of osteoarthritis has not yet been fully uncovered. With ongoing research, however, it has been gradually determined that OA is not caused solely by mechanical injury or aging, but rather involves chronic low-grade inflammation, metabolic imbalances, dysfunctional adaptive immunity, and alterations in central pain processing centers. The main risk factors for OA include obesity, age, gender, genetics, and sports injuries. In recent years, extensive research on gut microbiota has revealed that gut dysbiosis is associated with some common risk factors for OA, and that it may intervene in its pathogenesis through both direct and indirect mechanisms. Therefore, gut flora imbalance as a pathogenic factor in OA has become a hotspot topic of research, with potential therapeutic connotations. In this paper, we review the role of the gut microbiota in the pathogenesis of OA, describe its relationship with common OA risk factors, and address candidate gut microbiota markers for OA diagnosis. In addition, with focus on OA therapies, we discuss the effects of direct and indirect interventions targeting the gut microbiota, as well as the impact of gut bacteria on the efficacy of OA drugs.

Bioengineered Versatile Heterojunctions as Stress Busters Targeting Matrix Degradation and Ferroptosis for Osteoarthritis Therapy

Bioengineered Versatile Heterojunctions as Stress Busters Targeting Matrix Degradation and Ferroptosis for Osteoarthritis Therapy

Microvesicles Released by Osteoclastic Cells Exhibited Chondrogenic, Osteogenic, and Anti-Inflammatory Activities: An Evaluation of the Feasibility of Their Use for Treatment of Osteoarthritis in a Mouse Model

Extracellular vesicles (EVs), particularly exosomes (EXOs) of various skeletal and stem cells, were shown to delay osteoarthritis (OA) progression, and apoptotic bodies (ABs), another EV subtype, of osteoclasts showed osteoanabolic actions and were involved in the osteoclastic-regulation of local bone formation. Moreover, this study demonstrates that microvesicles (MVs) released by osteoclasts displayed potent pro-chondrogenic, pro-osteogenic, and anti-inflammatory activities. These activities were unique to osteoclastic MVs and were not shared by osteoclastic ABs and EXOs or MVs of other cell types. Because chronic synovial inflammation, progressive articular cartilage erosion, abnormal subchondral bone remodeling, and inability to regenerate articular cartilage are key etiologies of OA, we postulate that the foregoing activities of osteoclastic MVs could simultaneously target multiple etiologies of OA and could thereby be an effective therapy for OA. Accordingly, this study sought to assess the feasibility of an osteoclastic MV-based strategy for OA with a mouse tibial plateau injury model of OA. Briefly, tibial plateau injuries were created on the right knees of adult C57BL/6J mice, MVs were intraarticularly injected into the injured joints biweekly, and the OA progression was monitored histologically at five weeks post-injury. The MV treatment reduced the OA-induced losses of articular cartilage area and thickness, decreased irregularity in the articular cartilage surface, reduced loss of gliding/intermediate zone of articular cartilage, reduced osteophyte formation, suppressed synovial inflammation, and decreased the OARSI OA score. In summary, treatment with osteoclastic MVs delayed or reversed OA progression. Thus, this study supports the feasibility of an osteoclastic MV-based therapy for OA.

Effect of Hyaluronic Acid Compared to Platelet-Rich Plasma as Adjuvants to Bone Marrow Mesenchymal Stem Cell Treatment of Knee Osteoarthritis: Analysis from Two Clinical Trials

Background: Bone marrow mesenchymal stem cell (BM-MSC) therapy has emerged as a safe and feasible treatment option for patients with knee osteoarthritis (OA). However, the role of adjuvants remains unclear. Our aim was to evaluate the clinical and radiological effects of hyaluronic acid (HA) in comparison to platelet-rich plasma (PRP) as adjuvants to 100 × 106 BM-MSCs in the treatment of knee OA. Methods: We used data from two randomized, parallel-group and controlled clinical trials which tested the efficacy of BM-MSC, previously published in 2016 (Clinical Trials.gov identifier NCT02123368, Nº EudraCT: 2009-017624-72) and 2020 (Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23). Results: Of the 34 patients included in the study, 24 had received 100 × 106 BM-MSCs plus PRP and 10 had received 100 × 106 BM-MSCs plus HA. On average, BM-MSC plus HA showed a higher improvement in VAS for pain [β-coefficient: −1.25; 95% confidence interval (95% CI):−2.20 to −0.30) than BM-MSC plus PRP (p = 0.01). We also observed that BM-MSC plus HA showed a greater improvement in all the WOMAC subscales scores and in the WOMAC overall score, compared to BM-MSC plus PRP, although these differences were not statistically significant. The Whole-Organ Magnetic Resonance Imaging Score (WORMS) at 12 months was more beneficial with 100 × 106 BM-MSCs plus HA (β-coefficient: −12.61; 95% CI: −19.71, −5.52) than with BM-MSC plus PRP (p = 0.001). Conclusions: The clinical and radiological outcomes after BM-MSC therapy for knee OA could differ according to the adjuvant employed. HA showed greater clinical effectiveness and fewer instances of articular degeneration than PRP as an adjuvant.

Osteoarthritis associated with metabolic syndrome: epidemiology, pathogenesis, treatment

Metabolic syndrome (MS) is a complex of metabolic disorders, including insulin resistance, abdominal obesity, diabetes mellitus, hyperuricemia and arterial hypertension. According to the World Health Organization, the number of people with obesity worldwide is steadily increasing, taking on the characteristics of a “pandemic”. Against this backdrop, diseases pathogenetically linked to MS, such as osteoarthritis (OA), are gaining particular significance. Modern biochemical and molecular-genetic research has provided new data on the etiology and pathogenesis of OA, allowing the identification of phenotypes of the condition. One such phenotype is OA associated with MS, or metabolic OA. The development of this form of the disease is influenced by numerous factors, including hypersecretion of pro-inflammatory adipokines, transformation of synovial macrophages, direct effects of free fatty acids, biomechanical overload of joints, and others. Treatment of metabolic OA, in addition to standard approaches outlined in numerous clinical guidelines, has its own specific features. Particular emphasis is placed on weight reduction through lifestyle modification, strengthening of musculo-tendinous complexes, and concomitant therapy for metabolic disorders. These measures have demonstrated significant therapeutic effects, including pain reduction, decreased inflammation, and slowing of disease progression. One of the modern comprehensive remedies with phytonutritional components is Revocca capsules (“BIOTECHNOS”, Russia). Their composition in daily dosage includes phytosterols (calculated as β-sitosterol) at 100 mg, unsaponifiable compounds from avocado and soybean oils (in a 1:2 ratio) at 300 mg, rosehip extract at 300 mg, resveratrol at 70 mg, and zinc (as zinc citrate) at 12 mg. Given the increasing number of patients with the metabolic phenotype of OA, comprehensive hypolipidemic and anti-inflammatory therapy provided by multi-component drugs is becoming increasingly significant.

In Vivo and In Vitro Evaluation of the Feasibility and Safety Profiles of Intraarticular Transplantation of Mitochondria for Future Use as a Therapy for Osteoarthritis

In Vivo and In Vitro Evaluation of the Feasibility and Safety Profiles of Intraarticular Transplantation of Mitochondria for Future Use as a Therapy for Osteoarthritis

High-Throughput Screening Strategy and Metal-Organic Framework-Based Multifunctional Controlled-Release Nanomaterial for Osteoarthritis Therapy.

Osteoarthritis (OA) is a prevalent degenerative disease that lacks effective therapy. Oxidative stress is one of the major factors contributing to OA; however, treatments targeting oxidative stress are still lacking. In the current study, we established an oxidative stress-induced cell death model in chondrocytes in vitro and screened drugs that may suppress oxidative stress-induced cell death. Ethyl gallate (EG) was identified as the most potent drug against oxidative stress-induced cell death out of more than 600 drugs in the natural product library. Application of drugs without an appropriate delivery system for OA therapy may have drawbacks such as low bioavailability, short action time, and poor efficacy. Herein, poly-His6-zinc assembly (PZA), a pH-responsive metal-organic framework (MOF) loaded with EG (EG@PZA) was designed for OA therapy. It was demonstrated that EG@PZA may have the lysosome escape property, which dramatically increases the utilization of EG. Furthermore, EG@PZA showed enhanced release capability of EG in the acidic microenvironment. In vitro and in vivo studies demonstrated that EG@PZA effectively suppresses oxidative stress-induced extracellular matrix degradation, ferroptosis, and senescence in chondrocytes and also ameliorates OA in the destabilization of the medial meniscus (DMM) mouse model in vivo. Together, the current study showed that EG@PZA may become a potential controlled-release nanomaterial for effective OA therapy.

Danggui niantong decoction attenuates synovial fibrosis through regulating PI3k/AKT signaling pathway.

Danggui Niantong Decoction (DGNTD) is a traditional Chinese medicine compound formula that has been demonstrated to possess efficacy in the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), as well as for dispelling moisture and relieving pain. As mentioned before, DGNTD is essential for synovial inflammation in RA. The primary features of the OA synovial membrane are low-grade inflammation, hyperplasia with enhanced fibroblast-like synoviocytes (FLS) proliferation, and fibrosis, which can cause pain and stiffness. However, it is still unknown how DGNTD functions in the OA synovium. Clarify the influence of DGNTD on OA synovium and investigate potential mechanisms of action. The principal constituents of DGNTD were detected using liquid chromatography-mass spectrometry (LC-MS) analysis. To evaluate the effect of DGNTD on synovial inflammation and fibrosis, a transforming growth factor beta (TGF-β)-stimulated rat FLS cell model and a rat OA animal model based on anterior cruciate ligament transection (ACLT) and partial medial meniscectomy (MMx) were employed. Our results showed that 322 components were detected using LC-MS. In vivo, DGNTD therapy reduced pain, synovial inflammation, and fibrosis. The therapy significantly reduced levels of pain-related molecules, specifically calcitonin gene-related peptide (CGRP) and inducible nitric oxide synthase (iNOS), as well as fibrotic markers, including alpha smooth muscle actin (α-SMA) and type III collagen alpha-1 (Col3a1), in the synovium. A proteomics study demonstrated that DGNTD decreased the fibrotic protein Col3a1. DGNTD reduced the mRNA expression of pro-inflammatory and fibrotic markers (tumor necrosis factor alpha (TNF-α), interleukin-1 beta(IL-1β), interleukin-6(IL-6), α-SMA, Col3a1and TGF-β) in TGF-β-induced FLS. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and validation results revealed that DGNTD inhibits synovial fibrosis via the phosphatidylinositol 3-kinase (PI3K)/protein Kinase B (AKT) signaling pathway. DGNTD partially relieves pain, synovitis, and synovial fibrosis by regulating the PI3K/AKT pathway. These findings provide fresh information about the underlying mechanisms and successful therapy of OA, as well as a theoretical and experimental foundation for the clinical management of OA using DGNTD.

Comparison of Short-Term Effects of Extracorporeal Shock Wave Therapy, Low-Level Laser Therapy and Pulsed Electromagnetic Field Therapy in Knee Osteoarthritis: A Randomized Controlled Study.

Background: Knee osteoarthritis (OA) is the most prevalent form of osteoarthritis and a leading cause of chronic pain in adults. This study aimed to compare the short-term effects of extracorporeal shock wave therapy (ESWT), low-level laser therapy (LLLT), and pulsed electromagnetic field therapy (PEMF) on pain, function, and quality of life in patients with knee OA. Methods: A hundred and twenty patients with Kellgren-Lawrence grade 2-3 knee OA were randomized into four groups: ESWT (once a week for three sessions), LLLT (twice a week for eight sessions), PEMF (twice a week for eight sessions), and a control group with 30 patients in each group. All participants were instructed in a daily exercise program, including knee joint range of motion, stretching, and strengthening exercises (3 × 10 repetitions). Outcome measures, including the visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form-36 (SF-36), and the Timed Up and Go (TUG) test, were assessed at baseline after treatment and at the third month. Results: There were no significant differences between groups at baseline regarding VAS, WOMAC, SF-36, and TUG scores (p > 0.05). Significant improvements were observed in all parameters post-treatment for all groups (p < 0.001). However, the improvements in the PEMF group were significantly lower than in the ESWT and LLLT groups, particularly for VAS, WOMAC pain, and SF-36 physical function scores (p < 0.05). No significant differences were found between ESWT and LLLT (p > 0.05). Conclusions: In the short-term, ESWT, LLLT, and PEMF effectively reduce pain, improve physical function, and enhance quality of life in patients with knee OA, though PEMF showed less pronounced improvements.

Characterization and variability of PROMIS-10 scores with physical therapy in knee osteoarthritis: A retrospective review.

Knee osteoarthritis (OA) and its impairments affect patients' physical and mental health. Radiographically severe knee OA is believed to respond less to conservative treatments including physical therapy (PT) but has not been compared specifically with Patient-Reported Outcomes Measurement Information System (PROMIS)-10. To correlate baseline PROMIS-10 physical and mental health scores in patients undergoing PT for knee OA, subgrouped by radiographic severity (Kellgren-Lawrence [KL] grade and number of knee compartments involved). Additionally, to describe the relationship between radiographic severity of knee OA and the change in PROMIS-10 scores post-PT. Retrospective review. Outpatient musculoskeletal clinics at an orthopedic specialty hospital. One hundred nine patients (age ≥ 18 years) who presented for evaluation of knee OA from April 1, 2019 to August 1, 2021, had baseline radiographs, underwent PT, and completed PROMIS-10 at baseline and follow-up. PT. PROMIS-10 physical and mental health scores. Participants were 60% female; average age was 66.6 ± 10.0 years. Baseline PROMIS-10 physical and mental health scores averaged 44.4 ± 7.2 and 52.8 ± 9.0. Post-PT PROMIS-10 physical and mental health scores averaged 44.7 ± 6.7 and 52.6 ± 8.7. Physical health scores improved in 39% of patients; mental health scores improved in 36% of patients (no statistical significance). There was no relationship between post-PT PROMIS-10 scores and radiographic severity of knee OA. Females exhibited osteoarthritic changes in all compartments in 72% of cases compared to 55% of males (p = .020). Females demonstrated a higher predisposition for lateral compartment involvement (83% vs. 64%; p = .021) and a higher proportion of severe OA, radiographically, with a KL grade 3-4 (92% vs. 80%; p = .051). More than one third of patients with knee OA reported improved physical and mental health post-PT. The degree of benefit did not relate to radiographic severity. Although OA is characterized by radiographic measurements, there are variables beyond the radiographic imaging that may affect patient outcomes.

Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge. This study aims to develop fully characterized, reproducible, clinical-grade batches of sEV derived from umbilical cord (UC)-MSC for the treatment of OA while assessing its efficacy and safety. Initially, a standardized, research-grade manufacturing protocol was established to ensure consistent sEV production. UC-MSC-sEV characterization under non-cGMP conditions showed consistent miRNA and protein profiles, suggesting their potential for standardized manufacturing. In vitro studies evaluated the efficacy, safety, and potency of sEV; animal studies confirmed their effectiveness and safety. In vitro, UC-MSC-sEV polarized macrophages to an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating their potential to create an anti-inflammatory environment in the affected joints. In silico studies confirmed sEV's immunosuppressive signature through miRNA and proteome analysis. In an OA mouse model, sEV injected intra-articularly (IA) induced hyaline cartilage regeneration, validated by histological and μCT analyses. The unique detection of sEV signals within the knee joint over time highlights its safety profile by confirming the retention of sEV in the joint. The product development of UC-MSC-sEV involved refining, standardizing, and validating processes in compliance with GMP standards. The initial assessment of the safety of the clinical-grade product via IA administration in a first-in-human study showed no adverse effects after a 12 month follow-up period. These results support the progress of this sEV-based therapy in an early-phase clinical trial, the details of which are presented and discussed in this work. This study provides data on using UC-MSC-sEV as local therapy for OA, highlighting their regenerative and anti-inflammatory properties and safety in preclinical and a proof-of-principle clinical application.Graphical

Internal heat acupuncture therapy for 44 cases knee osteoarthritis of early to middle stages

To observe the clinical effect of internal heat acupuncture therapy for knee osteoarthritis of early to middle stages, and explore its influence on cartilage thickness. A total of 44 patients with knee osteoarthritis of early to middle stages were treated with internal heat acupuncture therapy at ashi points (most of them are located at the subpatellar fat pad, both sides of the patellar ligament, the tendon of the quadriceps and the attachment of the medial and lateral collateral ligaments), once a week, a total of 4 weeks of treatment. Before and after treatment, after 3 months of treatment completion (in the follow-up), the visual analogue scale (VAS) score, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score, frequency of 30-second chair stand test (30sCST), cartilage thickness of femoral intercondylar and knee joint ultrasound score were compared, and the clinical effect was evaluated. After treatment, the VAS、WOMAC and knee joint ultrasound scores were reduced (P<0.05), frequency of 30sCST was increased (P<0.05) compared with those before treatment; in the follow-up, the VAS、WOMAC scores were reduced (P<0.05), frequency of 30sCST and cartilage thickness of femoral intercondylar were increased (P<0.05) compared with those before treatment. After treatment, the total effective rate was 93.2% (41/44), in the follow-up, the total effective rate was 95.5% (42/44). Internal heat acupuncture therapy is effective in the treatment of knee osteoarthritis of early to middle stages, could relieve the pain, improve the joint function, and delay cartilage degeneration and disease progression.

Sequential Targeting Chondroitin Sulfate-Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages.

The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low-grade inflammation in joint-related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self-assembling, licofelone-loaded nanoparticle (termed LCF-CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation. LCF-CSBN is internalized by M1 macrophages via CD44-mediated endocytosis and targets the Golgi apparatus accompanied with the reactive oxygen species-responsive release of licofelone (LCF, dual inhibitor of arachidonic acid metabolism). LCF-CSBN effectively promotes M1 to M2 macrophage transition by reprogramming the Golgi apparatus-related sphingolipid metabolism and arachidonic acid metabolism. Intra-articularly injected LCF-CSBN retains in the joint for up to 28 days and accumulates into M1 macrophages. Moreover, LCF-CSBN can effectively attenuate joint inflammation, oxidative stress, and cartilage degeneration in OA model rats. These findings indicate the promising potential of lipid-metabolism-reprogramming LCF-CSBN in the targeted therapy of OA.

Two-Thirds Maintain High Adherence to Digital Education and Exercise Therapy With Comparable Outcomes Across Adherence Clusters: A Registry Study Including Data From Over 14 000 Patients in Sweden

OBJECTIVE: To explore trajectories of 12-week adherence to a digital education and exercise therapy for knee and hip osteoarthritis (OA), associations with baseline characteristics, and trajectories of patient-reported outcomes measures (PROMs) up to 1-year follow-up. DESIGN: Retrospective cohort (registry) study. METHODS: Weekly data on adherence (ie, the percentage of completed activities [exercises, lessons, and quizzes]) were obtained over 12 weeks (n = 14 097). Longitudinal k-means clustering was used to identify adherence trajectory clusters. Associations of baseline characteristics with adherence trajectory clusters were assessed using multinomial logistic regression. Trajectories of each PROM (pain, function, and general health) from baseline up to 1-year follow-up (measured at 3-month intervals) across adherence trajectory clusters were explored using generalized estimating equations adjusted for baseline characteristics. RESULTS: Four adherence trajectory clusters were identified: "high-persistent" (68.0%), "high-declining" (16.6%), "moderate-increasing" (8.5%), and "moderate-declining" (6.9%). Multinomial logistic regression suggested that female sex, older age, lower body mass index, lower education, living outside metropolitan cities, higher level of physical activity, less anxiety/depression, no fear of movement, having walking difficulties, and higher readiness to do exercise were associated with a higher probability of assignment to "high-persistent" than other clusters. Beliefs/perceptions and sociodemographic factors accounted for most of the explained variation in adherence trajectory clusters. While "high-persistent" cluster generally reported better outcomes than other clusters, these differences were small. CONCLUSION: While there were variations in adherence to the digital treatment, participants reported clinically comparable PROMs regardless of their adherence trajectory cluster. J Orthop Sports Phys Ther 2025;55(1):1-12. Epub 22 November 2024. doi:10.2519/jospt.2024.12864.

Alleviating osteoarthritis-induced damage through extracellular vesicles derived from inflammatory chondrocytes.

The role of extracellular vesicles (EVs) derived from inflammatory chondrocytes in EV-based therapy for osteoarthritis (OA) has received little attention. We examined the effects of EVs derived from both normal rat chondrocytes (nEVs) and IL-1β-treated rat chondrocytes (iEVs) on IL-1β-treated rat chondrocytes, macrophages, and osteoblasts, alongside mRNA-seq and miRNA-seq analyses of both them. Additionally, nEVs and iEVs were administered intra-articularly in the joints of rat models subjected to anterior cruciate ligament transection (ACLT), and the morphological alterations across the joints were assessed. These findings indicated that iEVs, compared with nEVs, significantly enhanced collagen II synthesis in IL-1β-treated chondrocytes, accompanied by marked increases in ER stress and autophagy. In comparison to nEVs, iEVs exhibited a greater effect on facilitating M2-type macrophage polarization while simultaneously diminishing M1-type polarization, a process likely mediated by the downregulation of chemotactic cytokines such as Cxcl10, Ccl5, Cxcl9, Cxcl1, and Cxcl11. iEVs exerted a more pronounced influence on the phenotypic characteristics of IL-1β-treated osteoblasts than nEVs. In the ACLT-rat model, iEVs, akin to nEVs, effectively mitigated articular cartilage degradation. However, there was no significant difference in OARSI Scores between the two groups, despite iEVs exerting a greater effect on increasing hyaline cartilage thickness and proteoglycan content. iEVs were superior to nEVs in attenuating synovium inflammation and promoting trabecula formation in the femur subchondral bone. Consequently, iEVs, akin to nEVs, significantly alleviated OA-induced damage. Moreover, iEVs outperformed nEVs in certain aspects, notably in augmenting hyaline cartilage, reducing synovium inflammation, and promoting trabecular formation in the subchondral bone during the early stage of OA.

Identification of Key Chondrocyte Apoptosis-Related Genes in Osteoarthritis Based on Weighted Gene Co-Expression Network Analysis and Experimental Verification.

Osteoarthritis (OA) is the primary cause of disability worldwide. Chondrocyte apoptosis has important implications for OA onset and progression. This work was designed to explore the mechanisms of chondrocyte apoptosis in OA and identify key chondrocyte apoptosis-related genes (CARGs). GSE32317 and GSE55235 datasets were acquired from the Gene Expression Omnibus (GEO) database. OA-associated module genes were determined via weighted gene co-expression network analysis (WGCNA) in GSE32317. CARGs were acquired from public databases. ClusterProfiler was employed for GO and KEGG analyses. Protein-protein interaction (PPI) network establishment was realized via the STRING database and Cytoscape, and the hub genes were screened by MCC, MNC, and DMNC algorithms of cyto-Hubba. The diagnostic values of the hub CARGs in OA in GSE55235 were verified via receiver operating characteristic (ROC) curve analysis. C28/I2 cells were stimulated with IL-1Β to establish the in vitro OA model. WGCNA identified 9,141 OA-related genes and 248 CARGs, resulting in 75 CARGs in OA. GO and KEGG analyses demonstrated that the 75 CARGs were primarily enriched in response to lipopolysaccharide, transcription regulator complex, and DNA-binding transcription factor binding, along with NF-kappa B and TNF signaling pathways. NFKB1 and ICAM1 were identified as the hub CARGs in OA through the three algorithms, which showed favorable prognostic values for OA. Notably, both bioinformatics analysis and in vitro assays revealed upregulated NFKB1 and ICAM1 expression in OA. NFKB1 and ICAM1 were the hub CARGs in OA, and might serve as diagnostic signatures and therapeutic targets for OA therapy.

A &lt;b&gt;Case Series Analysis of Trans-Arterial Embolization for Osteoarthritis-Related Hand Pain&lt;/b&gt;

Osteoarthritis (OA) is a widespread disorder which commonly impacts a significant portion of the population. Although most cases involve the knee joint, it can also affect the carpometacarpal joint and cause significant pain in the hand and thumb. Traditional treatments often provide short-term pain relief and need continual treatment prompting the need for exploring alternative therapies to prolong the duration of pain relief. This case series assesses the clinical success of trans-arterial embolization (TAE) of the joints in the hand as a minimally invasive treatment for chronic pain associated with hand joint OA, defined as a 50% (or greater) decrease in Visual Analog Scale (VAS) score overall, as well as a decrease in prescribed pain medication use. We present a case report of four patients who underwent this intervention for hand joint osteoarthritis. Preliminary results show an average decrease in VAS exceeding the 50% threshold, with a notable reduction in pain medication usage and improvements in daily activities. These findings suggest that TAE shows promise as a minimally invasive therapy for hand joint OA, warranting further investigation into its long-term efficacy and safety.