Management Of OA Research Articles

Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach

In this review, we seek to explore two distinct approaches to the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition to OA and generating early intervention options, and the retrospective approach, aimed at halting or reversing OA progression post-symptom onset. The clinical management of OA remains challenging, largely due to the limited availability of preventative treatments and failure of existing therapies to modify or reverse the underlying pathophysiology. The prospective approach involves the identification of genetic markers associated with OA and utilizes in vitro and in vivo models to characterize the underlying disease mechanism. Further, this approach focuses on identifying genetic predispositions and unique molecular subtypes of OA to develop individualized treatment plans based on patient genotypes. While the current literature investigating this strategy has been notable, this approach faces substantial challenges, such as extensive time burdens and utilization of extensive genetic testing that may not be economically feasible. Additionally, there is questionable justification for such extensive investigations, given OA’s relatively low mortality rates and burden when contrasted with diseases like specific forms of cancer, which rely heavily on the prospective approach. Alternatively, the retrospective approach primarily focuses on intervention following symptom onset and aims to utilize novel therapeutics to slow or reverse the inflammatory cascade typically seen in disease progression. These treatments, like Hippo pathway inhibitors, have shown initial promise in halting OA progression and alleviating OA symptomology by modulating cellular processes to preserve articular cartilage. In comparison to the prospective approach, the retrospective strategy is likely more cost-effective, more widely applicable, and does not necessitate thorough and invasive genetic screening. However, this approach must still be weighed against the typical natural history of disease progression, which frequently results in total knee arthroplasty and unacceptable outcomes for 15–20% of patients. From a comparative analysis of these two approaches, this review argues that the retrospective strategy, with ideally lower time and economic burden and greater accessibility, offers a more reasonable and effective solution in the context of OA management. Using a similar approach to other management of chronic diseases, we suggest an “Inverted Pyramid” model algorithm, a structured research and development regimen that prioritizes generating widely effective therapies first, with subsequent refinement of treatments based on the development of patient resistance to these therapies. We argue that this strategy may reduce the need for total knee arthroplasty while improving patient outcomes and accessibility.

Elevated Netrin-4 Expression and Its Action in Infrapatellar Fat Pad.

Knee osteoarthritis (KOA) is a degenerative joint disease characterized by inflammation and cartilage degradation. The infrapatellar fat pad (IFP), located beneath the patella within the knee joint, serves as a key anatomical structure involved in cushioning and supporting the knee. It is also an active endocrine organ that secretes various bioactive substances, potentially influencing the local inflammatory environment and contributing to KOA pathogenesis. Netrin-4 (NTN4), a protein primarily known for its role in neuronal guidance, has been implicated in various non-neuronal functions, including inflammatory processes and tissue remodeling. This study aims to explore the involvement of NTN4 in KOA, focusing on its expression in the IFP and its potential impact on disease progression. This study involved 82 patients with radiographically confirmed KOA undergoing total knee arthroplasty (TKA). The correlation between NTN4 expression and OA pathology, including Kellgren-Lawrence (K/L) grades, was investigated. NTN4-expressing cells were identified in the stromal vascular fraction, including fibroblastic, hematopoietic, and endothelial cells of the IFP. To elucidate the molecular effects of NTN4, RNA sequencing (RNA-seq) was performed on fibroblastic cells treated with recombinant NTN4. Subsequent quantitative PCR (qPCR) was used to validate the RNA-seq findings. NTN4 expression was significantly elevated in the IFP of patients with advanced KOA (K/L grades 3 and 4) compared to those with early-stage disease (K/L grade 2). Higher NTN4 expression was found in fibroblastic cells, and RNA-seq analysis revealed upregulation of genes associated with pro-inflammatory pathways, including IL-17 and TNF-α signaling, and matrix degradation. Notably, genes including IL6, MMP1, CXCL1, and CXCL8 were significantly elevated, as confirmed by qPCR, indicating NTN4's role in promoting an inflammatory and catabolic environment. Our findings suggest that NTN4 plays a significant role in the pathogenesis of KOA by promoting inflammation and matrix degradation within the IFP. Although NTN4 expression was not directly correlated with clinical symptoms, its elevated expression in fibroblastic cells and influence on inflammatory and degradative pathways suggest a potential mechanism for exacerbating joint damage. Targeting NTN4 could offer a novel therapeutic approach to mitigating inflammation and slowing disease progression in KOA, ultimately improving patient outcomes. Further research is needed to clarify NTN4's specific roles and therapeutic potential in OA management.

Successful Management of Waja’al-Rukba (Knee Osteoarthritis) with Unani Pharmacopeial Poultice: A Case Study

Knee osteoarthritis (Knee OA) is the most common Musculoskeletal disorder, which causes functional disability thus, increasing the economic burden in society. In Unani medicine knee Osteoarthritis is treated with various regimens and drugs. Among these regimens, Dimād (Poultice) is prepared with several single Unani pharmacopeial drugs that exert anti-inflammatory, analgesic and anti-arthritic actions. Keeping this in mind a case study was conducted to assess the efficacy of Dimād-i-jalinus a pharmacopeial Unani formulation in the management of Knee OA. A 63-year-old female patient with chief complaints of pain and swelling in the left knee joint, joint stiffness and mild tenderness feeling severe pain while performing daily activity for the last 6 months was treated at OPD of Hakim Syed Ziaul Hasan Govt. (Auto) Unani Medical College & Hospital, Bhopal. Dimād-i-jalinus was given to the patient, in paste form and the patient was explained to use this paste over the anterior surface of the Left knee joint and the bandage was wrapped to keep the medicines in place overnight every day for 14 days. The patient was assessed at baseline, 7th day and 14th day based on changes in subjective and objective parameters with the help of Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC). The present study reveals that Dimād-i-jalinus is safe and effective in treating Knee OA without any side effects. Therefore, further randomized clinical studies need to be carried out to validate the effectiveness of Dimād-i-jalinus in the management of Knee OA.

Critical evaluation of the current role of SYSADOA in the management of osteoarthritis (literature review)

Background. Osteoarthritis is a common chronic disease characterized by progressive degradation of all joint components and inflammation. The priority issue in the management of OA is sear­ching for drugs that simultaneously relieve symptoms, modify the course of the disease, and are safe for use. Symptoma­tic slow-ac­ting drugs (SYSADOA) are of considerable interest due to their potential to slow cartilage degeneration and potential osteoarthritis di­sease mo­difying effect. The purpose of the study was to ana­lyze current literature data on several types of SYSADOA, their biological role, mecha­nisms of effect on joints, effectiveness and safetye. ­Materials and methods. An analytical review of literature data was conducted using the ana­lysis of scientific databases PubMed, Web of Science, Scopus, Google Scholar for the period 2005–2024, the search was conducted using the keywords “osteoarthritis”, “SYSADOA”, “DMOAD”, “effectiveness”, “safety”. Results. Glucosamine salts (GA) and chondroitin sulfate (CS) are the most stu­died slow-acting drugs and have positive biological effects on joint tissues. Prescription salts of GA and CS have effect of pain relieve and joint function improvement as separate agents and also potentiate the effect in combination. Studies revealed limiting of cartilage volume loss and joint space narrowing – a potential DMOAD effect of these drugs. GA salts and CS drugs are safe, as they have no difference in the frequency of side effects compared to placebo. The quality of drugs largely depends on the type of raw materials and technological production process, which are not standardized now. Conclusions. The role of SYSADOA in the treatment of OA has not been definitively determined, and studies on the effectiveness of drugs such as SYSADOA and the study of their DMOAD effect are still ongoing. Further stu­dies should focus on the use of pharmacological class SYSADOA that have been properly purified and quality strictly supervised.

Annual Trends of High Tibial Osteotomy: Analysis of an Official Registry in Italy.

Background and Objectives: Knee osteoarthritis is a serious burden for modern countries. Timing of surgery and treatment choice are still a matter of controversy in the orthopedic literature. The purpose of this study was to ascertain the incidence and hospitalization trends of high tibial osteotomy in Italy from 2001 to 2016. Materials and Methods: Data are sourced from the National Hospital Discharge Reports (SDO) of the Italian Ministry of Health between 2001 and 2016. Results: A total of 34,402 high tibial osteotomies were performed over the study period in Italy. The cumulative incidence was 3.6 cases per 100,000 residents. The age classes 50-54, 55-59 showed the higher number of procedures. In pediatric patients (0-19 years), high tibial osteotomies are also largely performed. The majority of patients having surgery were men with a M/F ratio of 1.5. The mean age of patients was 44.2 ± 19.2 years. Males were significantly younger than females (43.3 ± 20.7 vs. 45.6 ± 17.7). The average length of hospitalization was 6.1 ± 7.3 days. Over the course of the analysis, a declining trend in hospital stay length was seen. The main primary diagnosis codes were "Varus knee" (736.42 ICD-9-CM code, 33.9%), "Osteoarthrosis, localized, primary, leg region" (715.16 ICD-9-CM code, 9.5%). Conclusions: Over the study period, high tibial osteotomies in Italy almost halved. Varus deformity and knee osteoarthritis are the leading causes requiring high tibial osteotomy. Except for the pediatric setting, results showed that from the 20-24 age class to the 50-54 age class, there was an increasing request for knee osteotomy, whereas in those aged >60 years, the incidence progressively decreased. The evident decline in HTO performed over the years in Italy seems to reflect a minor role for knee osteotomy in the management of knee OA, as it seems to be primarily reserved for younger male patients.

Barriers, facilitators and referral patterns of general practitioners, physiotherapists, and people with osteoarthritis to exercise

BackgroundBarriers and facilitators of general practitioners (GPs), physiotherapists (PTs), and people with hip and knee osteoarthritis (PwOA) may influence uptake of and referral to guideline-based exercise treatments for OA. ObjectiveTo identify barriers and facilitators of GPs, PTs and PwOA to uptake of and referral to exercise treatments for OA. MethodsAn online survey was circulated to GPs, PTs, and PwOA in Ireland from March to September 2021. Data were collected on demographics, barriers and facilitators, and referral patterns to exercise treatments for OA. Frequency distributions were used to illustrate demographics, barriers and facilitators, and referral patterns to exercise treatments for OA. Results388 stakeholders responded (GPs = 148; PTs = 154; PwOA = 86). Barriers and facilitators were related to (1) stakeholder (e.g., patient tiredness and fatigue), (2) healthcare setting (e.g., appropriate referrals from GP or other sources), and (3) treatment (e.g., low-cost community-based exercise programmes) factors. While 91% of GPs would refer PwOA to physiotherapy if no barriers existed, only 60% would in their current practice. Only 33% of PwOA reported receiving a GP referral to physiotherapy. ConclusionStakeholder, healthcare setting and treatment barriers and facilitators of GPs, PTs, and PwOA influence uptake of and referral to exercise treatments for OA. Future strategies Future strategies addressing these factors may improve implementation of guideline-based management for OA. Contribution of the Paper•Despite an established evidence-based consensus, uptake of and referral to exercise as a first-line treatment for OA is suboptimal, partly influenced by the barriers and facilitators of stakeholders (e.g., GPs, PTs, and PwOA).•Barriers and facilitators that influence uptake of and referral to exercise treatments for OA are related to stakeholder, healthcare setting, and treatment factors.•Majority of PwOA are not receiving GP referrals to physiotherapy, and a mismatch between GPs intentions to and actual referrals to physiotherapy exists, primarily due to long waitlists to access services.•These findings may be adapted to inform strategies for the successful implementation of exercise treatments that are effective in encouraging guideline-based management of OA.

Microalgae‐Based Dual Drug Delivery System with Enhanced Articular Cavity Retention for Osteoarthritis Treatment

AbstractOsteoarthritis (OA) is a prevalent degenerative joint disease globally, and the availability of effective treatments for OA remains limited. Recent research has shown that metformin offers pleiotropic advantages in the development of OA. However, the therapeutic effects of metformin are hindered by inadequate residence time within the joints, instability, and low bioavailability. In this study, the utilization of natural microalgae S. platensis (SP) is proposed as carriers for metformin, resulting in the development of a metformin delivery system (SP@Met) as a dual drug delivery system that exhibits responsive dual drug cascade release and improved retention within the articular cavity. The local administration of SP@Met has demonstrated efficacy in extending the drug retention time within the articular cavity, while also enabling cascade release of both metformin and phycocyanin. SP@Met can effectively eliminate reactive oxygen species, reduce the expression of pro‐inflammatory cytokines, and restore the balance of cartilage anabolism and catabolism, thereby impeding the progression of OA. This therapeutic approach utilizes a natural microalgae carrier to facilitate efficient delivery of metformin to the articular cavity, resulting in synergistic therapeutic efficacy and offering a promising avenue for the management of OA for potential clinical application.

The role of dietary preferences in osteoarthritis: a Mendelian randomization study using genome-wide association analysis data from the UK Biobank.

To understand the impact of individual preferences for specific dietary items on OA, and to help inform the development of effective and targeted OA prevention and management strategies, we performed a Mendelian randomization analysis between dietary preferences and osteoarthritis. This study utilized genetic data from the UK Biobank to investigate the association between OA and 21 different common dietary items. Instrumental variables representing European populations were carefully selected based on their genetic significance and linkage disequilibrium. In cases where a dietary item had few relevant genetic markers, a more lenient selection threshold was applied. To prevent bias, the analysis excluded single nucleotide polymorphisms (SNPs) associated with factors such as body mass index (BMI) and cholesterol. Using inverse-variance weighting (IVW) and Mendelian randomization, significant associations were detected between certain dietary items and OA. Using Mendelian randomization to examine the relationship between 21 different dietary items and OA, significant associations were found for coffee, peas, watercress, and cheese, where the first two had a promoting effect and the last two an inhibiting effect on OA. Due to heterogeneity in the test results for cheese, a random IVW representation was used. The results of sensitivity analysis showed no significant heterogeneity or horizontal pleiotropy in the selected SNPS, demonstrating the reliability of Mendelian randomization analysis. This study identified coffee, peas, watercress, and cheese as food items that may have significant dietary effects on osteoarthritis. This information may be useful to consider in the development of OA management strategies.

Elucidation of the key therapeutic targets and potential mechanisms of Andrographolide multi-targets against osteoarthritis via network pharmacological analysis and experimental validation

ObjectiveOur purpose is to unveil Andrographolide's potential multi-target and multi-mechanism therapeutic effects in treating OA via systematic network pharmacological analysis and cell experimental validation. Materials and MethodsInitially, we gathered data from Andrographolide and OA-related databases to obtain information on Andrographolide's biological properties and the targets linked with OA. We developed a bioinformatic network about Andrographolide and OA, whereby we analyzed the network to identify potential therapeutic targets and mechanisms of action of Andrographolide. Subsequently, we used molecular docking to analyze the binding sites of Andrographolide to the target proteins. At the same time, SDF-1 was used to construct an OA cell model to verify the therapeutic effect of Andrographolide on OA and its effect on target proteins. ResultsOur experimental results show that Andrographolide has excellent pharmaceutical properties, by Lipinski's rules for drugs, suggesting that this compound can be considered to have a high therapeutic potential in drug development. 233 targets were preliminarily investigated, the mechanisms through which Andrographolide targets OA primarily involve the TNF signaling pathway, PI3K-AKT signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. These mechanisms target OA by influencing immune and inflammatory responses in the joints, regulating apoptosis to prevent chondrocyte death. Finally, TNF-α, STAT3, TP53, IL-6, JUN, IL-1β, HIF-1α, TGF-β1, and AKT1 were identified as 9 key targets of Andrographolide anti-OA. In addition, our molecular docking analyzes with cell experimental validation further confirm the network pharmacology results. According to our molecular docking results, Andrographolide can bind to all the hub target proteins and has a good binding ability (binding energy < -5 kcal/mol), with the strongest binding affinity to AKT1 of −9.2 kcal/ mol. The results of cell experiments showed that Andrographolide treatment significantly increased the cell viability and the expression of COL2A1 and ACAN proteins. Moreover, 30 μM Andrographolide significantly reversed SDF-1-induced increases in the protein expression of TNF-α, STAT3, TP53, IL-6, JUN, IL-1β, HIF-1α, and TGF-β1, and decreases in the protein expression of AKT1. ConclusionThis study provides a comprehensive understanding of the potential therapeutic targets and mechanisms of action of Andrographolide in OA treatment. Our findings suggest that Andrographolide is a promising candidate for drug development in the management of OA.

Is Quadriceps-Strengthening Exercises (QSE) in Medial-Compartment Knee Osteoarthritis with Neutral and Varus Malalignment a Paradox? - A Risk-Appraisal of Strength-Training on Disease Progression.

The present inquiry seeks to investigate whether the current regimens of QSEs (Quadriceps-Strengthening Exercises) aggravate the disease while mitigating symptoms. A comparative study was conducted on 32 patients with medial compartment osteoarthritis of knees. While the neutral group of 16 patients was constituted of those with an anatomical-lateral-femoro-tibial-angle (aFTA) 176-180º, varus group comprised an equal number of patients with an aFTA >180º. A home-based 12-week strength-training program involving weekly visits to hospital for supervised sessions was administered. The outcome measures were visual-analog-scale (VAS), medial patello-femoral joint tenderness (MPFJT), time-up-and-go-test (TUGT), stair-climb test, step test, WOMAC, IKDC scores, aFTA, hip-knee-ankle (HKA) angle, lateral-tibio-femoral-joint-separation (LTFJS), and horizontal-distance-from-centre-of-knee-to-Mikulicz-line. There was a significant increase in quadriceps strength (p<0.01) in both groups. Values for neutral group with VAS score (p=0.01), MPFJT (p=0.01), TUGT (p=0.01), timing of the stair climb test (p=0.01), WOMAC (p<0.01), and IKDC (p=0.03) were better compared to varus group with VAS score (p=0.13), MPFJT (p=0.03), TUGT (p=0.90), timing of stair climb test (p=0.68), WOMAC (p<0.02), and IKDC (p=0.05). Varus group also showed an increase in aFTA and LTFJS in 12 patients, increase in HKA in 11, and increase in horizontal distance from the centre of knee to the Mikulicz line in 7 patients. The present study brings to the fore the paradoxical role played by QSEs in management of medial knee OA. While there is a radiological progression of the disease in both neutral and varus mal-aligned knees more so in the latter than the former.

Therapeutic effectiveness of oral homeopathic remedy in management of knee osteoarthritis via attenuation of oxidative and inflammatory pathway

Background Osteoarthritis (OA) is the most common prevalent condition that affects joints and causes erosion of the cartilage. Many conventional medications show evidence of short-term effectiveness. However, they are associated with numerous adverse effects. Objective As homeopathy is a complementary modality, thus this study aimed to explore the therapeutic effectiveness of homeopathic remedies in management of knee OA that proved efficiency in management of knee OA without health hazards. Patients and methods Thirty cases (25 females, five males) were complaining of bilateral grade 2 or 3 knee OA were included in the study. Each patient was taken as her/his control. One milliliter of a diluted complex of four homeopathic remedies (Arnica Montana, Ledum Palustre, Rhus Tox, and Ruta Graveolens) was taken orally by each patient for 6 weeks in ascending potency. Results All clinical parameters showed significant improvement after the end of therapy. Visual analog scale, number of tender points, tenderness score (TS), angle of knee flexion, heel to hip distance Western Ontario and McMaster universities osteoarthritis index score and Lequesne index (P≤0.05). In addition, there was significant improvement in laboratory markers as significant increase in serum enkephalin and interleukin-4 and decreasing in erythrocyte sedimentation rate (P≤0.05). Conclusion The study showed efficiency of four homeopathic remedies in decreasing pain, tenderness, improving knee flexion and quality of life supported with improvement in serum levels of encephalin, interleukin-4 and erythrocyte sedimentation rate in grade 2 or 3 OA patients.

Epigenetics in Knee Osteoarthritis: A 2020-2023 Update Systematic Review.

Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation.

PDK4 inhibits osteoarthritis progression by activating the PPAR pathway

BackgroundOsteoarthritis (OA) is a degenerative joint disease caused by the deterioration of cartilage. However, the underlying mechanisms of OA pathogenesis remain elusive.MethodsHub genes were screened by bioinformatics analysis based on the GSE114007 and GSE169077 datasets. The Sprague–Dawley (SD) rat model of OA was constructed by intra-articular injection of a mixture of papain and L-cysteine. Hematoxylin–eosin (HE) staining was used to detect pathological changes in OA rat models. Inflammatory cytokine levels in serum were measured employing the enzyme-linked immunosorbent assay (ELISA). The reverse transcription quantitative PCR (RT-qPCR) was implemented to assess the hub gene expressions in OA rat models. The roles of PDK4 and the mechanism regulating the PPAR pathway were evaluated through western blot, cell counting kit-8 (CCK-8), ELISA, and flow cytometry assays in C28/I2 chondrocytes induced by IL-1β.ResultsSix hub genes were identified, of which COL1A1, POSTN, FAP, and CDH11 expressions were elevated, while PDK4 and ANGPTL4 were reduced in OA. Overexpression of PDK4 inhibited apoptosis, inflammatory cytokine levels (TNF-α, IL-8, and IL-6), and extracellular matrix (ECM) degradation protein expressions (MMP-3, MMP-13, and ADAMTS-4) in IL-1β-induced chondrocytes. Further investigation revealed that PDK4 promoted the expression of PPAR signaling pathway-related proteins: PPARA, PPARD, and ACSL1. Additionally, GW9662, an inhibitor of the PPAR pathway, significantly counteracted the inhibitory effect of PDK4 overexpression on IL-1β-induced chondrocytes.ConclusionPDK4 inhibits OA development by activating the PPAR pathway, which provides new insights into the OA management.

Effect of Zimad (Unani pharmacopeial liniment) in the management of Knee osteoarthritis: A case study

Knee osteoarthritis (Knee OA) is the most common Musculo-skeletal disorder, which causes functional disability thus, increasing the economic burden in the society. In conventional medicine it has been treated with various drugs i.e., NSAIDs, cox inhibitors and steroids. Although these drugs pose only symptomatic relief. In Unani medicine Osteoarthritis is treated with variety of regimens and drugs. Among these regimens Zimad (liniments) prepared with number of single Unani pharmacopeial drugs that exert anti-inflammatory, analgesic and anti-arthritic actions. Keeping this in mind a case study was conducted to assess the efficacy of Zimad containing drugs including Zingiber officinale Rosc, Saussurea lappa, Colchimum autumnale, Myristica fragrans Houtt and Matricara chamomile in the management of Knee OA for 14 sittings of alternate application for 28 days. A female patient with chief complaints of pain in left knee joint, along with the swelling, joint stiffness and mild tenderness feeling severe pain while performing daily activity for last 8 months was treated at IPD of the AKTC, AMU, Aligarh. The patient was assessed at baseline, 14th day and 28th day on the basis of changes in subjective and objective parameters. At the end of the treatment patient got significant relief in subjective (pain, joint stiffness and ROM) and objective parameters (VAS and WOMAC). The present study reveals that Zimad is safe and effective in the treatment of Knee OA without any side effect. Therefore, further randomized clinical studies need to be carried out to validate the effectiveness of Zimad in the management of Knee OA.&#x0D; Keywords: Ilaj Bit Tadbeer, Knee osteoarthritis, Sesquiterpene lactone, Waja’ al-Rukba, Zimad, Zingiberene

Upregulation of cIAP1 induced by AZD8330 alleviates osteoarthritis progression by inhibiting the RIP1-associated necrosis signaling pathway

BackgroundOsteoarthritis (OA) is a prevalent degenerative joint disease [1]. It has come to light that AZD8330 can suppress the generation of proinflammatory factors and deter the inflammatory response [2]. Given that inflammation is a primary causative factor in OA, it is posited that AZD8330 might exhibit superior efficacy in OA management. MethodsIn this study, we investigated the potential of intraperitoneal injection of AZD8330 to retard the progression of osteoarthritis in a murine model with surgically induced medial meniscus destruction (DMM). Concurrently, we employed ATDC5 cartilage cells to dissect the mechanism through which AZD8330 inhibits the TNF-α-induced NF-κB signaling pathway via modulation of RIP1. The findings revealed that AZD8330 mitigated cartilage degradation and the inflammatory response, leading to a substantial reduction in OARSI scores among DMM mice treated with AZD8330. Mechanistically, AZD8330 functioned as a suppressor of the TNF-α-induced NF-κB/p65 signaling pathway by facilitating the phosphorylation activation of cIAP1-mediated RIP1. The combination of data from both in vivo and in vitro experiments supports the conclusion that AZD8330 can attenuate chondrocyte degradation, thereby alleviating OA, by regulating the NF-κB/P65 signaling pathway through modulation of RIP1 activity. Consequently, the utilization of AZD8330 may hold potential in the prophylaxis of osteoarthritis. ResultsOur investigation delineates the role of AZD8330 in the regulation of inflammation in the context of OA treatment. Furthermore, we have unveiled that the inhibitory impact of AZD8330 on OA may hinge upon the activation of cIAP1, which in turn downregulates RIP1, thereby restraining the NF-κB/P65 signaling pathway. This study lends credence to the notion that AZD8330 may be a promising contender for osteoarthritis therapy. ConclusionsOur study provides compelling evidence attesting to the capacity of AZD8330 in managing inflammation within the realm of OA treatment. Likewise, our study has elucidated that the attenuation of OA by AZD8330 relies on the activation of cIAP1 to inhibit RIP1, consequently suppressing the NF-κB signaling pathway. On the strength of our present study, we may have identified a viable drug candidate for OA treatment.

Phage Display Identified Peptide with Selectivity for Human Osteoarthritic Chondrocytes

AbstractOsteoarthritis (OA) is one of the most common joint disorders in western populations, affecting millions of people worldwide and with a rising incidence as life expectancy continues to increase. Current therapies for OA management fail to halt the progressive degradation of articular cartilage, urging the need for more effective therapies to improve cartilage function and enhance patient's quality of life. Through phage display technology, biopanning on a population of heterogenous chondrocyte cells isolated from six different OA donors, and using a random 12‐amino acid peptide phage library, a peptide selective for human OA chondrocytes (GFQMISNNVYMR) is identified. A twofold increase in fluorescence intensity is observed for OA chondrocytes, compared to normal chondrocytes, when cells are incubated with the identified peptide conjugated to a fluorescent label, being selectively internalized by OA cells. The identified peptide can be further modified and exploited for developing early diagnostic of OA and/or improve drug delivery to target cells through peptide‐drug conjugates.

Health-Related Quality of Life and Associated Factors Among Patients With Knee Osteoarthritis.

Knee osteoarthritis, a chronic degenerative disease, is becoming a public health problem around the world due to increasing life expectancy. We aimed to assess the impact of knee osteoarthritis on the quality of life (QoL) of the patients and to identify factors associated with impaired QoL. We conducted a cross-sectional monocentric study including patients with knee osteoarthritis. The pain was evaluated by the Visual Analog Scale (VAS). The short form of the Knee injury and Osteoarthritis Outcome Score (KOOS-PS) was used to assess functional impact. QoL was assessed using the OsteoArthritis of Knee Hip Quality Of Life (OAKHQOL) questionnaire. Fifty patients were included. The mean age of patients was 59 ± 9 years. The sex ratio was 0.25. At least one comorbidity was noted in 77% of patients. The mean disease duration was 8.82 years. Mean VAS pain and KOOS-PS were 6.8 ± 1.1 and 54.7 ± 9.6/100; respectively. Assessment of the QoL by OAKHQOL showed impaired QoL in all domains; the worst scores concerned the areas of social functioning and pain. Factors associated with an altered QoL were age > 65 years, longer disease duration, higher pain intensity, comorbidities, and functional impairment. Our patients showed an impaired QoL in all domains, particularly in terms of physical activity and social functioning. Lower QoL scores were associated with age, comorbidities, pain, function, and disease duration. Factors associated with QoL should be considered in the management program of these patients. Screening and the treatment of comorbidities are also useful for the management of knee OA.

Investigating the Efficacy and Safety of Diacerein in the Management of Knee Osteoarthritis with reference to its conventional management.

Designated as a "priority disease" by World Health Organization, Osteoarthritis is the most common chronic rheumatic disease. Providing a proper treatment for Osteoarthritis is still a major public health challenge. Diacerein has been proposed as a slow acting, symptom modifying or even disease modifying drug used in Osteoarthritis having a risk-benefit ratio far better than conventionally used drugs. However, the evidence of efficacy and safety of use of Diacerein in Osteoarthritis is yet to be explored. Hence, this study attempted to investigate the efficacy and safety of Diacerein in the management of knee osteoarthritis. This is an analytical cohort study comparing Diacerein with Non-steroidal anti-inflammatory drugs for two months in the management of knee OA. Efficacy was assessed by scores of Lysholm Knee Scoring Scale, Knee injury and Osteoarthritis Outcome Score - Physical Function Short form and Western Ontario and McMaster Universities Osteoarthritis Index. After two months of treatment, the post- treatment scores were significantly superior to the baseline scores in both the treatment groups (p<0.001). There were no significant differences among the post-treatment scores in two different treatment groups (p>0.05). Discoloration of urine and gastritis were the frequently reported adverse effects in Diacerein treatment group and Non-steroidal anti-inflammatory drugs treatment group respectively. Our findings have shown Diacerein is as effective as Non-steroidal anti-inflammatory drugs in treating knee OA patients. Diacerein was generally well tolerated, with a good safety profile. These findings indicate the need for further studies with experimental study design in larger scale.

The potential role of synovial cells in the progression and treatment of osteoarthritis.

Osteoarthritis (OA), the commonest arthritis, is characterized by the progressive destruction of cartilage, leading to disability. The Current early clinical treatment strategy for OA often centers on anti-inflammatory or analgesia medication, weight loss, improved muscular function and articular cartilage repair. Although these treatments can relieve symptoms, OA tends to be progressive, and most patients require arthroplasty at the terminal stages of OA. Recent studies have shown a close correlation between joint pain, inflammation, cartilage destruction and synovial cells. Consequently, understanding the potential mechanisms associated with the action of synovial cells in OA could be beneficial for the clinical management of OA. Therefore, this review comprehensively describes the biological functions of synovial cells, the synovium, together with the pathological changes of synovial cells in OA, and the interaction between the cartilage and synovium, which is lacking in the present literature. Additionally, therapeutic approaches based on synovial cells for OA treatment are further discussed from a clinical perspective, highlighting a new direction in the treatment of OA.

Factors Influencing Surgical Decision Making in Trapeziometacarpal Osteoarthritis

With trapeziometacarpal osteoarthritis (TMC OA), the relationship between disease severity and pretreatment dysfunction, patient expectations, and preferred patient treatment and management remains unclear. This study aimed to assess the association between functional status, pretreatment expectations, and demographic and clinical characteristics of TMC OA patients who decide to undergo operative management. Patients diagnosed with TMC OA (n= 96) were administered the Thumb Arthritis Expectations Survey and the Brief Michigan Hand Questionnaire (bMHQ) during their initial office visit. Demographic data (sex, age, race, education level, marital status, comorbidities, and hand dominance) and clinical characteristics (prior injury, and therapeutic interventions including splinting, steroid injections, therapy, and anti-inflammatory medication) were collected. Multiple logistic regression was used to assess the association between surgical treatment and expectation scores. Our logistic regression model found that lower bMHQ scores, high thumb arthritis expectation survey scores, and prior treatments for TMC OA were associated significantly with the surgical treatment of TMC OA. After controlling for all possible covariates, the odds of having surgery was 3.9 times higher among patients with high expectations (above median) compared to patients with low expectations (adjusted odds ratio [AOR], 3.9; 95% confidence interval [CI], 1.3-11.2). Patients with average function, as measured by bMHQ scores, were 74.5% less likely to elect for surgery than those with the lowest bMHQ (AOR, 0.3; 95% CI, 0.1-0.9). Patients treated previously with steroids were 13 times more likely to elect for surgery than those who were never treated for TMC arthritis (AOR,13.1; 95% CI, 2.2-77.0). Patients with TMC OA who elect to proceed with surgical management have lower bMHQ (greater perceived dysfunction) and higher expectations, and have had prior treatment. Age was not a significant predictor of surgical management of TMC OA. Prognostic IV.