Progression Of Osteoarthritis Research Articles

Collection, Establishment and Assessment of Complex Human Osteocartilaginous Explants for Modeling Osteoarthritis.

With the increasing burden of osteoarthritis worldwide, cost efficient and reliable models are needed to enable the development of innovative therapies or therapeutic interventions. Ex vivo models have been identified as valuable modalities in translational research, bridging the gap between in vitro and in vivo models. Osteocartilaginous explants from Osteoarthritis (OA) patients offer an exquisite opportunity for studying OA progression and testing novel therapies. We describe the protocol for establishing human osteocartilaginous explants with or without co-culture of homologous synovial tissue. Furthermore, a detailed protocol for the assessment of explanted tissue in terms of protein content using Western blot and immunohistochemistry is provided. Commentaries regarding the technique of choice, possible variations and expected results are inserted.

Resatovir Combined with Glycyrrhizic Acid Ameliorates Osteoarthritis and Enhances Autophagy in Chondrocytes

Background Osteoarthritis (OA) is a chronic disease worldwide. With resatovir usually used as an inhibitor, resatovir and glycyrrhizic acid have several pharmacological activities. Purpose We intend to explore the mechanism underlying resatovir combined with glycyrrhizic acid in OA. Methods After the establishment of an animal model of OA through anterior cruciate ligament transection and destabilization of the medial meniscus, the rats were subjected to intramuscular injection of resatovir combined with glycyrrhizic acid (60 mg/kg) or 5% glucose (60 mg/kg) every day for 4 weeks. During the progress, the rat movement and the bend score of knees were observed through behavioral studies. Additionally, the SKP2 gene expression and toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)-related signaling pathways were examined, as apoptosis and autophagy were evaluated by flow cytometry. Results With increased inflammatory cells in the model group, treatment with resatovir combined with glycyrrhizic acid significantly decreased the number of inflammatory cells. Meanwhile, the treatment resulted in decreased SKP2 expression in OA cells when hindering the migration of preosteoclast cells. Interestingly, it was observed that the bend score increased over the treatment with resatovir plus glycyrrhizic acid and TIPPI% declined dramatically. Resatovir treatment enhanced autophagy and apoptosis in OA cells and decreased pP65, P65, and LC3 expression. Conclusion Resatovir combined with glycyrrhizic acid can inhibit the inflammatory response through decreasing SKP2 expression and induce autophagy activation in OA cells through TLR4/NF-κB signaling, thereby attenuating OA progression.

Impact of Aging and Knee Osteoarthritis on Lower Limb Alignment and CPAK Classification: Gender Differences in a Japanese Cohort.

Objective: This study investigates the impact of age and knee osteoarthritis (OA) on the coronal plane alignment of the lower extremity in Japanese males and females, utilizing the Coronal Plane Alignment of the Knee (CPAK) classification system. Methods: A cross-sectional analysis was conducted with 150 male and 150 female patients. Participants were divided into three groups according to age and OA progression. The mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured using standard digital long-leg radiographs. Arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated, and the CPAK classification was performed to verify the distribution among the three groups. Results: The results showed increased varus alignment of the mean mLDFA correlated with OA in both genders and with aging in males. The mean mMPTA did not change in males but shifted toward varus in females with both aging and OA. Both genders demonstrated a constitutional varus alignment with the progression of osteoarthritis (males: 1.3 ± 2.4° to -3.5 ± 3.7°, p < 0.001; females: -1.2 ± 3.2° to -3.6 ± 2.9°, p < 0.001). However, this trend with aging was observed only in females (0.0 ± 2.5° to -1.2 ± 3.2°, p = 0.018). JLO maintained its apex distal position with aging and OA progression in all subjects. The study further revealed a notable transition from CPAK Type II to Type I with OA progression in both genders, additionally influenced by aging in females. Conclusions: Aging affects coronal alignment and CPAK classification differently across genders. With OA progression, there was a shift toward smaller aHKA, while JLO remained unchanged. Compared to other races, young Japanese people exhibit similar CPAK distributions, but distinct differences appear in OA-affected individuals, highlighting potential racial variations in CPAK classifications.

Femoroacetabular Impingement: A Literature Review

Femoroacetabular impingement (FAI) is a hip condition characterized by abnormal contact between the femoral head and the acetabulum, often leading to joint damage and osteoarthritis. This literature review explores the pathophysiology, diagnosis, and treatment options for FAI, synthesizing current research findings from clinical and biomechanical studies. FAI is classified into two primary types: cam impingement, caused by deformity of the femoral head, and pincer impingement, due to acetabular over-coverage. Mixed types involving both mechanisms are also common. Advancements in imaging modalities, such as MRI and CT, have improved diagnostic accuracy, allowing for earlier detection and better differentiation between types of FAI. Conservative treatment options, including physical therapy and anti-inflammatory medications, are often first-line therapies. However, surgical intervention, particularly arthroscopy, has gained prominence for symptomatic patients, demonstrating favorable outcomes in restoring hip function and delaying the progression of osteoarthritis. Despite the success of surgical interventions, challenges remain in understanding the long-term outcomes, particularly concerning the recurrence of symptoms and the risk of joint degeneration. This review also highlights controversies regarding the optimal management of asymptomatic FAI, as the risk-benefit balance of surgical treatment in such cases remains unclear. Overall, FAI remains a significant clinical issue requiring a multidisciplinary approach to optimize patient outcomes, and further longitudinal studies are necessary to assess the efficacy of treatment strategies over time. Keywords: Femoroacetabular, Impingement, Joint

Machine Learning Model Trained with Finite Element Modeling Can Predict the Risk of Osteoarthritis: Data from the Osteoarthritis Initiative

Objective: Despite long simulation times, recently developed finite element analysis (FEA) models of knee joints have demonstrated their suitability for predicting individual risk of onset and progression of knee osteoarthritis. Therefore, the objective of this study was to assess the feasibility of machine learning (ML) to replicate outcomes obtained from FEA when simulating mechanical responses and predicting cartilage degeneration within the knee joint.Design: Two ML models based on the Gaussian Process Regression (GPR) algorithms were developed. The first model (GPR1) utilized age, weight, and anatomical joint dimensions as predictor variables to predict tissue mechanical responses and cartilage degeneration based on FEA data. The second model (GPR2) utilized age, weight, height, and gender to predict anatomical joint dimensions, which were then used as inputs in the GPR1 model. Finally, the GPR1 and combined GPR1+GPR2 models were used to investigate the importance of clinical imaging when making personalized predictions for knees from healthy subjects with no history of knee injuries.Results: In the GPR1 model, R2 of 0.9 was exceeded for most of the predicted mechanical parameters. The GPR2 model was able to predict knee shape with R2 of 0.67–0.9. Both GPR1 and combined GPR1+GPR2 models offered equally good performances (AUC = 0.73–0.74) in classifying patients at high risk for the onset and development of knee osteoarthritis.Conclusions: In the future, real-time and easy-to-use GPR models may provide a rapid technology to evaluate mechanical responses within the knee for researchers or clinicians who have no former knowledge of FEA.

Targeted non-invasive Metformin-Curcumin co-loaded nanohyaluosomes halt osteoarthritis progression and improve articular cartilage structure: A preclinical study

Osteoarthritis (OA) is a degenerative disease that affects the quality of life in elderly and young populations. Current therapies using corticosteroids and non-steroidal anti-inflammatory drugs via parenteral or oral routes show limited ability to retard progression of the disease and achieve long term effectiveness and safety. Herein, the potential of MT-Cur combinatorial nano-formulations in OA management was explored for the first time. MT-Cur loaded nanohyaluosomes (MT-Cur-HL1) were designed for topical administration of the combined therapy in OA. The optimized MT-Cur-HL1 showed particle size 247.7 ± 3.7 nm, zeta potential −37.3 ± 0.4 mV; and entrapment efficiency (%EE) 70.22 %±0.303 and 76.7 %±0.077 for MT and Cur, respectively. MT-Cur-HL1 exhibited sustained drug release over 24 h and were stable over 3 months at 4 °C in terms of P.S., ZP and %EE. A detailed preclinical study, using MIA-induced osteoarthritis rat model, revealed the most significant anti-arthritic effect and halted OA progression of MT-Cur-HL1. This was proved to be mainly through the potentiation of p-AMPK signaling that ultimately led to suppression of its downstream TLR4/ NF-κB signaling pathway with subsequent reduction in MMP13 and ADAMTS5 induced chondrocytes degeneration. This study proved that this trajectory effectively promotes a significant improvement in the articular cartilage structure and reinforcement of joint mobility with an efficient antinociceptive effect. In conclusion, the novel MT-Cur coloaded nanohyaluosomes offer a promising non-invasive approach for the local management of OA.

The Presentation, Clinical Diagnosis, Risk Factors, and Management of Rapidly Progressive Hip Osteoarthritis: A Narrative Literature Review.

Rapidly progressive hip osteoarthritis (RPOH) is a rare and severe form of osteoarthritis (OA), marked by the rapid degeneration and destruction of the femoral head, often within months. Despite its unclear etiology, several factors such as subchondral fractures and immune responses have been proposed as possible contributors. This narrative review aims to synthesize current knowledge on the pathogenesis, risk factors, clinical presentation, imaging features, and grading systems of RPOH. Predominantly affecting elderly females, RPOH presents distinctive challenges in both diagnosis and management due to its abrupt onset and severity. Known risk factors include advanced age, female gender, obesity, intra-articular corticosteroids use, and long-term hemodialysis. Clinically, RPOH is characterized by severe pain during active weight-bearing movements, despite patients presenting a normal range of motion during passive examination in the early stages. While several classification systems exist, there is no universal standard, complicating differential diagnosis and clinical approaches. This review emphasizes the necessity for early diagnostic methods utilizing specific biomarkers, rapid differential diagnosis, and targeted, personalized interventions based on individual risk factors.

Association of vertebral fractures with worsening degenerative changes of the spine: a longitudinal study.

Vertebral compression fractures (VFs) and spinal degeneration are both common causes of back pain, particularly in older adults. Previous cross-sectional studies have shown a potential association between these entities, but there is limited evidence on the role of VFs in spinal degeneration. In this longitudinal study, we evaluated the association between prevalent VFs and the subsequent progression of facet joint osteoarthritis (FJOA) and intervertebral disc height narrowing (DHN), using data from the Framingham Heart Study Offspring and Third Generation Multi-Detector Computed Tomography study. Summary indices representing the total burden of each spinal parameter (VFs, DHN and FJOA) were calculated for each individual. We hypothesized that prevalent VFs are associated with worsening spinal degeneration. 370 (31%) of 1197 participants, had a baseline (prevalent) VF. The change in summary index of DHN over the follow-up period was significantly higher in those with versus without prevalent VF (difference in change in DHN 0.38, 95% CI 0.18 to 0.59, P<.001), but the change in summary index of FJOA was similar between those with and without prevalent VF. However, once adjusted for age, sex, cohort, smoking status, body mass index, and baseline DHN, the change in summary index of DHN did not differ by prevalent VF status. There was a modestly higher change in the FJOA summary index in those with prevalent VFs compared to those without in the fully adjusted model (difference in change in FJOA 0.62, 95% CI -0.01 to 1.24, P=.054), driven primarily by those with severe (grade 3) VF (difference in change in FJOA 4.48, 95% CI 1.99 to 6.97). Moreover, there was greater change in the summary index of FJOA with increasing severity of prevalent VF (linear trend P=.005). Beyond the established morbidity and mortality associated with VFs, our study suggests that VFs may also lead to worsening spine osteoarthritis.

Medial Joint Opening in the Operated Knee After Unilateral High Tibial Osteotomy: Risk of Osteoarthritis and Future Surgery in the Operated and Nonoperated Knee

Background: High tibial osteotomy (HTO) modifies the mechanics of the affected knee but can also affect the nonoperated knee. However, no research has reported on the prognosis and risk factors related to the nonoperated knee after unilateral HTO. Purpose: To assess the radiological parameters associated with osteoarthritis (OA) progression and the need for surgery in the nonoperated knee after unilateral HTO, with concurrent assessment of the operated knee. Study Design: Case series; Level of evidence, 4. Methods: The medical charts of 197 patients with knee OA who underwent unilateral HTO between March 2007 and December 2020 were retrospectively investigated. Radiological parameters such as the Kellgren-Lawrence grade, weightbearing line ratio, joint line convergence angle (JLCA), and joint line obliquity angle were assessed preoperatively and 1 year postoperatively. Results: The mean follow-up length for the 197 patients was 5.9 ± 3.2 years for the operated knee and 5.5 ± 3.2 years for the nonoperated knee. A smaller postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .027) and undergoing surgery (P = .006) in the nonoperated knee. Conversely, a larger postoperative JLCA in the operated knee was a significant risk factor for OA progression (P = .014) and conversion to arthroplasty (P = .027) in the operated knee. A postoperative JLCA >1.5° (P < .001) and <3.9° (P < .001) was needed to reduce the risk of undergoing surgery in the nonoperated knee and OA progression in the operated knee, respectively. Additionally, a pre- to postoperative change in the JLCA (ΔJLCA) between −5.6° and −1.7° (P = .021 and P = .004, respectively) was needed to reduce the risk of OA progression in both knees. Conclusion: A large medial joint opening (a small postoperative JLCA) in the operated knee after unilateral HTO was associated with a higher risk of OA progression and surgery in the nonoperated knee. Conversely, a small medial joint opening (a large postoperative JLCA) was associated with a higher risk of OA progression and conversion to arthroplasty in the operated knee. For a balanced medial joint opening, if the postoperative JLCA was between 1.5° and 3.9° or the ΔJLCA was between −5.6° and −1.7°, a favorable prognosis in both knees could be anticipated.

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

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

CHANGES IN LIPID AND CARBOHYDRATE METABOLISM IN PATIENTS WITH OSTEOARTHRITIS WITH ACCOMPANYING ARTERIAL HYPERTENSION AND TYPE 2 DIABETES, DEPENDING ON BSMI VDR GENE POLYMORPHISM

It is known that Osteoarthritis (OA) is a common chronic disease of the musculoskeletal system, which leads to a significant loss of working capacity and disability of people of working age, which worsens the quality of life of the population and causes economic burden and losses to all countries of the world. In addition, OA is known as a disease with an inherent high level of comorbidity. Scientists single out diseases of cardiovascular diseases, digestive systems and metabolic disorders as those that are most often combined with OA and complicate the course of each other in manifestations, diagnostic and treatment processes. Today, modern science needs to understand the presence of a common genetic origin. It is known that the polymorphic variant of the VDR vitamin D receptor gene has a predisposition to common osteochondral diseases. However, the issue of participation in pathogenetic mechanisms of development and progression remains controversial. A polymorphic variant of the VDR gene has a predisposition to osteochondral diseases. However, its involvement in the pathogenetic mechanisms of the development and progression of osteoarthritis remains controversial, therefore The aim of the study is to investigate the specifics of the impact of comorbid pathology on carbohydrate and lipid metabolism and the state of the vascular wall in patients with osteoarthritis, taking into account the polymorphic variant of the VDR gene (Bsml, rs1544410). Object and research methods. 100 patients were examined and also divided into groups: 1st group – patients with OA; II – OA with arterial hypertension; ІІІ – OA, arterial hypertension (AG) and type 2 diabetes mellitus, a blood sample was taken and, depending on age, comorbidity, the presence of the polymorphic variant BsmI (rs1544410) of the VDR gene, indicators of carbohydrate and lipid metabolism, the level of end metabolites of nitric oxide and endothelin-1 were studied and the impact on radiological changes and the functional state of the knee joints was evaluated. Control – 30 people. Results of the study and their discussion. It has been established that osteoarthritis is characteristic of persons of working age. With increasing age, it is characteristic to be burdened by comorbid pathologies with worsening of the course of the main disease. Expected violation of carbohydrate metabolism was observed in the III group of patients, although dynamic probable changes were also in the II group (p&lt;0.05). Lipid metabolism in the I group was probably higher than the group of control, but was within the physiological norm, while groups II and III had significant pathological changes compared to the indicators of the I group and practically healthy persons. Hypercholesterolemia became a trigger for a decrease in the total level of stable total nitrogen monoxide metabolites and an increase in endothelin-1, which forms endothelial dysfunction and leads to the progression of AG and worsening of the course of OA. After the genotyping and division into genotypes of the polymorphic variant BsmI of the VDR gene, conclusions were obtained about the unfavorable allele A in the exchange processes of the above indicators. Conclusions. Features of violations of carbohydrate and lipid metabolism, the condition of the endothelium, against the background of comorbidity and the presence of an unfavorable allele A of the BsmI polymorphic variant of the VDR gene should be taken into account in the complex diagnostic and treatment process of patients with OA.

Macrophage Membrane-Biomimetic Multi-Layered Nanoparticles Targeting Synovial Angiogenesis for Osteoarthritis Therapy.

Osteoarthritis (OA) is an inflammatory and progressive joint disease characterized by angiogenesis-mediated sustained, chronic, and low-grade synovitis. Anti-angiogenesis is emerging as a strategy for attenuating OA progression, but is often compromised by poor targeted drug delivery and immune clearance. Recent studies have identified macrophages formed a "protective barrier" in the lining layer (LL) of synovium, which blocked the communication of joint cavity and sublining layer (SL) of synovium. Inspired by natural mimicry, macrophage membrane-camouflaged drug delivery is explored to avoid immune clearance. Based on the single cell RNA sequencing, the CD34+ synovial cells are identified as "sentinel cells" for synovium angiogenesis. Consequently, CD34 antibody-modified macrophage membraneis constructed to target new angiogenesis. Hence, a biomimetic multi-layered nanoparticle (NP) is developed that incorporates axitinib-loaded poly(lactic-co-glycolic) acid (PLGA) with CD34 antibody modified macrophage membrane (Atb@NP@Raw@CD34) to specifically deliver axitinib (Atb) to the SL and sustain inhibiting angiogenesis without immune elimination. It is found that the Atb@NP@Raw@CD34 can pass through macrophage "barrier", specifically targeting CD34+ cells, continuously releasing Atb and anti-angiogenesis in OA synovitis. Furthermore, in vivo data demonstrated that Atb@NP@Raw@CD34 can attenuate joint degeneration by inhibiting synovium angiogenesis-mediated synovitis. In conclusion, local injection of Atb@NP@Raw@CD34 presents a promising approach for clinically impeding OA progression.

Sonographic Verification and Clinical Significance of the Features of Surrounding Structures in Knee Osteoarthritis

Background: Osteoarthritis (OA) of the knee joint is one of the most dangerous diseases, the most significant manifestation of which is chronic pain syndrome. There is a low correlation between the radiographic stage of OA and pain progression. First of all, this is a variety of pain syndromes, among which is the pathology of periarticular structures (AS). To date, the contribution of this type to the clinical picture of OA has been sufficiently studied, primarily due to the fact that the list and frequency of these lesions have not yet been described.Aim: to describe the basis of the main periarticular structures in patients with different radiographic stages of knee OA according to ultrasound data.Materials and methods: The observational study has currently included 88 patients who had an outpatient appointment with a rheumatologist for knee osteoarthritis between 2021 and 2023. The study assessed 110 knee joints using clinical and ultrasound techniques.Results: The most common periarticular ultrasound changes, regardless of radiographic stage, were pes anserine tendinopathy (57.3 %), Baker’s cyst (45.5 %), fibrosis of the severe Hoffa body (40 %) and ligamentopathy of the medial collateral ligament (36). ,4). %). A significant correlation was found between the number of changes according to ultrasound and the radiological stage (ρ=0.45 [95 % CI: 0.28, 0.59], p &lt;0.001) as well as between the VAS and the definition of identified ultrasound changes (ρ= 0.29 [95 % CI: 0.11, p=0.002); In addition, it was shown that late stages of OA are associated with a greater content of changes (p &lt;0.001).Conclusion: Changes in periarticular structures are present in most patients with knee osteoarthritis; their number correlates with the VAS value and radiographic stage of OA. Details of these changes, their clinical significance and pathogenetic contribution to the progression of knee OA require further study.

Enhanced joint pain in diabetic patients with knee osteoarthritis is associated with increased synovitis, synovial immune cell infiltration, and erythrocyte extravasation.

Diabetes mellitus (DM) is an important risk factor for the development of osteoarthritis (OA), increasing OA progression and OA pain. To gain insight into the underlying mechanisms of how DM exacerbates OA processes and OA pain, this study analyzed histological differences of synovial tissues from non-DM and DM patients with OA and correlated these differences with knee pain severity. Synovial tissue was obtained from 12 non-DM and 10 DM patients with advanced knee OA who underwent total knee arthroplasty. Synovial inflammation was assessed using the Synovitis score developed by Krenn. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess knee pain intensity and disability in OA patients. The number of mast cells, macrophages, nerve fibers, capillaries, larger vessels and erythrocyte extravasation were analyzed microscopically in histological and immunostained synovial sections from non-DM and DM patients. Association analyses were performed to determine associations between OA knee pain and synovial changes affected by DM. Synovial tissue from OA patients with DM had a higher synovitis score, more erythrocyte extravasation, and contained higher numbers of mast cells and macrophages compared to non-DM patients. The number of capillaries and vessels in the lining/sublining layer of the synovial tissue was reduced in DM patients. OA patients with DM had more severe knee pain compared to non-DM patients. The KOOS pain score was associated with the synovitis score, the number of tissue macrophages, and the number of mast cells in the synovial tissue (adjusted for age, sex, and BMI). In addition, the erythrocyte extravasation score was associated with the KOOS pain score and with the synovitis score. The study suggests that increased OA progression and pain severity in patients with DM result from more pronounced synovitis and synovial vascular leakage and increased infiltration of macrophages and mast cells.

Development of a novel rabbit model for femoroacetabular impingement through surgically induced acetabular overcoverage.

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra-articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra-articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6-month-old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center-edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real-time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C-KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.

Modulation of IFN-γ induced macrophage inflammatory responses via indomethacin-loaded NLCs for OA management

Macrophages are the main cells present in the synovial membrane. They play an important role in the development and progression of osteoarthritis (OA). After the establishment of the disease macrophages mostly adopt a pro-inflammatory secretory phenotype (OA phenotype) further inducing cartilage degradation. Indomethacin (IND) is a non-steroidal anti-inflammatory drug (NSAID) able to inhibit the synthesis of prostaglandins mediated by both cyclooxygenase isoforms depicting a potent anti-inflammatory capacity. However, the lack of specificity and short half-like of free drugs within the joint cavity limits its utility in controlling inflammation after intra-articular administration. This study aims at developing IND loaded glycosylated nanostructured lipid carriers (NLCs) to selectively target macrophages and promote their reprogramming to an anti-inflammatory phenotype. This approach focused on the local administration of the NLCs, offers a promising therapeutic strategy for treating OA by modulating the inflammatory environment within the joint. NLCs will be designed by combining experimental and in silico docking analyses, and thoroughly characterized to obtain drug delivery systems with high stability and suitable physicochemical properties. The proposed mannose-functionalized systems exhibited adequate particle sizes (≈ 70 nm) and positive surface charges (> 20 mV) to be efficiently retained in the joint cavity. Moreover, the developed NLCs demonstrated effective and specific uptake by OA-like macrophages leading to a significant decrease in the secretion of the pro-inflammatory cytokines IL-6, IL-8 and TNF-α similarly to the free drug. Therefore, these systems effectively reprogrammed OA-associated macrophages to adopt a more regenerative phenotype, offering a promising strategy for managing inflammation in OA.

A RANKL-UCHL1-sCD13 negative feedback loop limits osteoclastogenesis in subchondral bone to prevent osteoarthritis progression

Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.

Current issues in osteoarthritis treatment

Background: Osteoarthritis (OA) is the most prevalent chronic joint disorder that leads to pain, disability, and functional impairment. The OA prevalence among those aged ≥65 years in Korea was 30.2% between 2017 and 2021. Owing to a rapidly aging population, OA is becoming a significant public health and socioeconomic concern.Current Concepts: The onset of OA is characterized by cartilage injury, which affects the surrounding tissues and progresses to joint destruction. The pathophysiology varies across joints; hand OA is associated with genetic factors, whereas knee and hip OA are associated with mechanical stress. Nonsteroidal anti-inflammatory drugs are the primary treatment; however, considering their adverse effects and limited efficacy in halting disease progression, further research is warranted for more effective therapies. Natural medicines have been investigated; however, their clinical efficacy is inadequate.Discussion and Conclusion: Currently, no disease-modifying treatments are validated for OA. Animal models fail to reflect the slow progression and complexity of human OA; therefore, drug development remains challenging. In view of increasing healthcare costs and rapid population aging, further research and broader socioeconomic strategies are essential to manage the growing burden of OA.

Osteoarthritis After Anterior Cruciate Ligament Reconstruction: A Systematic Review of Contributing Factors and Potential Treatments.

Anterior cruciate ligament (ACL) injuries result in abnormal knee motion and long-term joint degradation. ACL reconstruction (ACLR) is done with the aim of restoring normal knee kinematics and slowing the joint degradation process. It does appear that this inevitably happens and can be impacted by a multitude of factors. The aim of this review was to examine the factors that influence the progression of osteoarthritis (OA) after ACLR and examine possible treatments that can aid in slowing that progression. A systematic review was conducted by searching all levels of evidence for all studies in English that assessed risk factors for developing OA after ACL reconstruction, had a minimum follow-up of 10 years, and used radiographical outcomes to measure the presence of OA. Studies on trial treatments to reduce osteoarthritis after ACL reconstruction were also included. It was found that among the factors associated with an increased risk of post-ACLR OA are meniscal lesions, meniscectomy, increased age at the time of ACLR, increased time from injury to surgery, male sex, reduced range of motion, smaller thigh girth, graft complications, and failure. Additionally, in performing the ACLR, anteromedial femoral tunnel placement, higher graft tension, and following guidelines for performing anatomic ACLR have been shown to reduce the risk of OA as well. Patients should be adequately counselled on their risk pre-operatively for informed decision-making. Surgeons should also be aware of potential risk factors and how they can be mitigated.

Efficacy of disease-modifying osteoarthritis drugs in the treatment of osteoarthritis

Background: Osteoarthritis is the most common form of chronic inflammatory arthritis, and its prevalence is steadily increasing owing to its association with aging. Therefore, understanding and implementing appropriate treatments for osteoarthritis in clinical practice is becoming increasingly important. Additionally, there is active research on a new approach for treating osteoarthritis: disease-modifying osteoarthritis drugs (DMOADs).Current Concepts: Several global osteoarthritis treatment guidelines exist; this article introduces the guidelines of the American College of Rheumatology and Osteoarthritis Research Society International, which are among the most widely recognized. A common theme across various guidelines is that exercise and weight loss are the primary recommended treatments. As for pharmacotherapy, the top recommendations include topical nonsteroidal anti-inflammatory drugs (NSAIDs) and oral NSAIDs. Although multiple classes of drugs such as DMOADs are being actively researched to slow the progression of osteoarthritis, no drug has yet been confirmed to be clinically effective or approved for use.Discussion and Conclusion: A deeper understanding of osteoarthritis treatment can help prevent malpractice and improve patient outcomes. While current treatments focus primarily on symptom management, the development of effective DMOADs holds promise for fundamentally altering the disease course and improving joint function and quality of life.