Osteoarthritis Patients Research Articles

Osteopontin as a biomarker for diagnosing the severity of osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis. It is characterized by the loss of cartilage and pain ultimately leading to difficulty in movement. Glycoprotein osteopontin (OPN) is an essential regulator that plays a critical role in developing osteoarthritis. The study aims to determine the level of OPN in the serum of patients with OA and its correlation with the content of calcium (Ca), phosphorus (P), and magnesium (Mg). The study was conducted on 92 male and female patients aged between 30 and 65, categorized into mild, moderate, and severe groups through clinical examination and X-rays. The control group consist of 58 healthy males and females 30-65-year old. OPN was measured using the ELISA technique, and minerals were estimated using spectrophotometry. It was shown that in OA patients, OPN level increased highly significant when compared with the control group (10.7 ± 3.4 ng/ml) and depended on OA severity. In patients with severe OA, it was higher (47.5 ± 8.1 ng/ml) than in groups with moderate (14.8 ± 4.5 ng/ml) and mild (12.1 ± 3.1 ng/ml) extent of the disease. We showed a significant positive relationship between OPN and phosphorus levels and a negative significant correlation between OPN and calcium, calcium/phosphorus ratio, and magnesium. These findings underscore the potential of OPN as a valuable biomarker for diagnosing the severity of osteoarthritis and monitoring the effectiveness of treatment. Keywords: calcium, magnesium, osteoarthritis, osteopontin, phosphorus.

The interplay between osteoarthritis and osteoporosis: Mechanisms, implications, and treatment considerations – A narrative review

This comprehensive review examines the relationship between osteoarthritis (OA) and osteoporosis (OP), two common disorders in the elderly. OA involves joint cartilage degeneration and pain, while OP leads to fractures due to reduced bone mass. Despite different pathologies, both conditions share risk factors such as age and genetics. Studies reveal mixed results: some show higher bone mineral density (BMD) in OA patients, suggesting an inverse relationship, while others find no significant link. Proposed mechanisms include mechanical loading, bone remodeling, and inflammation. Clinical strategies focus on maintaining bone health in OA and monitoring joint health in OP, with treatments like bisphosphonates and exercise. Understanding these interactions is crucial for developing integrated treatments to improve patient outcomes and quality of life. Further research is needed to clarify these complex mechanisms.

Knowledge, attitude, and practice toward nonsteroidal anti-inflammatory drugs among osteoarthritis patients: a cross-sectional study

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0–24), 18.12 ± 1.99 (possible range: 5–35), and 29.20 ± 5.52 (possible range: 10–50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (β = 0.978, P < 0.001). For individuals not using NSAIDs, the attitude had a direct effect on practice (β = 0.936, P < 0.001). Conclusion This study suggested that adequate NSAID knowledge is the prerequisite for correct NSAID-related medical decisions, while attitude has a crucial intermediary effect. Healthcare professionals and society should strengthen education regarding the relevant knowledge of NSAIDs and guide the cultivation of positive attitudes toward NSAIDs.

Long-term result of unicompartmental knee arthroplasty in knee osteoarthritis secondary to chondrodysplasia

Background. In determining the indications for unicondylar endoprosthesis of the knee joint the literature practically does not cover the results of such interventions in knee osteoarthritis in patients with chondrodysplasia. The purpose of our report was to publish our observation of the long-term results of unicondylar endoprosthesis of the knee joint in a patient with knee osteoarthritis due to chondrodysplasia. Material and methods. We operated on a patient with chondrodysplasia who came to the clinic at the age of 28 with complaints of pain in the right knee joint during walking, “clicking” and joint swelling. The radiological and magnetic resonance examination results of the right knee determined the presence of an area of aseptic necrosis of the medial femoral condyle. Considering the concordance of lower limb axis disorders, it was decided to perform unicondylar arthroplasty with preservation of the preoperative varus deformity to maintain the motor stereotype's compensation state. Results. In the postoperative period, there were no complications in wound healing, the rate of recovery of movements corresponded to similar indicators in patients with knee osteoarthritis of other etiologies after similar interventions, and the patient was discharged from the hospital on the sixth day after surgery with the preoperative range of motion in the operated joint. At the examination 10 years after the operation there were no complaints from the operated knee joint, the movements in the operated joint remained in the same range, and the patient moved without additional support with full load on the operated limb. Conclusions. Our results indicate the appropriateness of unicompartmental knee arthroplasty in patients with knee osteoarthritis secondary to.

Bioactive Compounds and Their Chondroprotective Effects for Osteoarthritis Amelioration: A Focus on Nanotherapeutic Strategies, Epigenetic Modifications, and Gut Microbiota

In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration.

Intraarticular hip corticosteroid injections offer no meaningful benefit in delaying time to total hip arthroplasty in patients with hip osteoarthritis

IntroductionSymptomatic hip osteoarthritis (OA) causes significant morbidity and functional limitations. While corticosteroid injections (CSI) are commonly offered and administered for OA pain relief, it is unknown if they offer any clinically meaningful long-term benefit or reduce the overall need for surgical intervention.MethodsA cross-sectional retrospective cohort study was performed on primary hip osteoarthritis patients from a single academic tertiary-care center arthroplasty clinic from 2014 to 2019. Patients were divided into three groups. CSI + THA: hip CSI patients who underwent subsequent ipsilateral THA. CSI-noTHA: hip CSI who have not had ipsilateral THA to date. THA-noCSI: a control group of consecutive hip OA patients who underwent primary THA without prior CSI. Demographic variables, injection relief duration, and radiographic arthritis severity were recorded. Time from clinic presentation to injection and/or THA were compared.Results357 patients met inclusion criteria and underwent guided, arthroplasty provider-ordered CSI. Mean duration of relief was 6.7 weeks (SD 8.7). 244 injection patients (67.2%) subsequently underwent THA (CSI + THA). 150 of 390 patients have not undergone THA at mean of 25.5 months follow-up. Mean time from clinic presentation to THA was 8.6 months longer after CSI (16.3, SD 17.8) months in CSI patients compared to 7.7 (SD 10.6) months for patients without CSI (p < 0.001). Of 117 patients in the CSI-noTHA group at mean 25 months follow-up, only 43 (12% of all injection patients) had not had THA because they found injections effective. The remaining 74 (63%) of CSI-noTHA patients have been deemed medically unfit for surgery or are currently scheduled for THA.Discussion/ConclusionThe results of this study suggest the utilization of intra-articular CSI as conservative treatment in an arthroplasty clinic does not prolong time to THA for a clinically important duration. The use of CSI should be reserved for diagnostic purposes and/or short-term pain relief in poor surgical candidates.Level of evidenceIII.

Spatiotemporal gait characteristics post-total hip arthroplasty and its impact on locomotive syndrome: a before-after comparative study in hip osteoarthritis patients.

Understanding the gait pattern of patients eligible for total hip arthroplasty (THA) due to hip osteoarthritis (OA) offers valuable information for improving locomotive syndrome (LS). This study aims to measure the gait patterns of THA-eligible patients using an optical motion capture system and to analyze these patterns using principal component analysis (PCA). Additionally, this study examines the relationship between THA-induced gait patterns and LS. This before-after study included 237 patients who underwent unilateral primary THA due to hip OA. The primary outcome measures were spatiotemporal gait parameters. Secondary outcome measures included three LS risk tests: a stand-up test, a two-step test, a 25-question Geriatric Locomotive Function Scale (GLFS-25), and total clinical decision limits stages. PCA was performed using 16 spatiotemporal gait parameters collected before and three months after THA. Principal components (PC) were selected to achieve a cumulative contribution rate of 90% (0.9) or higher. Each summarized PC was compared using a paired t-test before and three months after THA. Furthermore, multiple regression analysis was conducted to determine how changes in each PC between before and three months after THA related to changes in the four LS evaluation items. PCA identified three principal components (PC1, PC2, PC3) that accounted for a cumulative contribution rate of 0.910 using 16 spatiotemporal gait parameters. When comparing before and three months after THA for all three PCs, significant differences were observed in each PC (p<0.001), with overall walking ability and stance phase being higher three months after THA than before THA, while the asymmetry of support time was lower three months after THA. The results of multiple regression analysis revealed that PC1, PC2, and PC3 were the most influential factors in total clinical decision limits stage. For each LS risk test, the factors related to the stand-up test were identified as PC1, PC2, and PC3, while the factors related to the two-step test were identified as PC1 and PC2. The factors related to the GLFS-25 were also identified as PC1 and PC2. The most important findings of this study indicate that the three PCs represent over 90% of the 16 spatiotemporal gait parameters, which are associated with total clinical decision limits stage and LS risk tests. The present results suggest that PC1 represents overall walking ability, PC2 represents the stance phase, and PC3 represents asymmetry of support time. Gait pattern characteristics, such as overall walking ability, stance phase, and asymmetry of support time, were clearly defined by these PCs. Regarding the relationship between PC and LS, all three PCs are related to total clinical decision limits stage. In addition, PC1 and PC2 related to all three LS risk tests, and PC3 related only to the stand-up test.

The Immunomodulatory Effects of Curcumin on Forkhead Box O1 and MicroRNA-873 in Patients with Osteoarthritis

Osteoarthritis (OA) is among the most prevalent articular disorders, whose incidence is directly related to aging. Due to the antiinflammatory potential of curcumin as the active component of turmeric, the present study evaluated the effects of curcumin on the expression of genes related to T helper 17 (Th17), including forkhead box p3 (FOXP3), forkhead box o1 (FOXO1), transforming growth factor-β (TGFB1) and microRNA-873, human (HSA-MIR-873), in OA patients. Female patients with knee OA (n=30) were randomly categorized into 2 groups, including the intervention group who received curcumin (n=15) and the placebo (n=15) in a double-blind clinical trial for 3 months. The expression of FOXO1, FOXP3, TGFB1, and HSA-MIR-873 genes was evaluated by SYBR Green real-time reverse transcription polymerase chain reaction. In the curcumin group, FOXO1 gene expression was significantly increased, while the increase in FOXP3 gene expression was not significant. Moreover, the expression level of the HSA-MIR-873 gene showed a significant increase in the curcumin group. The modulatory effects of curcumin on Th17 function might be associated with the expression of FOXO1 and HSA-MIR-873 genes.

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.

The effectiveness of vitamin D supplementation in patients with end-stage knee osteoarthritis: Study protocol for a double-blinded, randomized controlled trial.

Osteoarthritis (OA) knee is one of the most common chronic degenerative conditions that imposes clinical and economic burdens on individuals and societies worldwide. Previous studies showed vitamin D levels correlated positively with lean muscle mass and grip strength, implying that vitamin D supplementation may improve muscle health in knee OA subjects. This randomized controlled trial (RCT) aims to compare the effects of vitamin D supplementation on knee muscle strength, physical function, pain, and sarcopenia status in patients with end-stage knee OA. Patients and outcome assessors will be blinded to group allocation. Fifty-six end-stage knee OA patients with vitamin D insufficiency fulfilling our inclusion criteria will be invited to participate in this study. Patients will be randomly assigned to take vitamin D supplementation (4,000 IU capsule daily) or placebo for six months. Measurements will be taken at baseline, three and six-month after the commencement of the vitamin D supplement, and 6-month after the interventional period. The primary outcome includes the isometric quadriceps and hamstring muscle strength measured by a hand-held dynamometer. Secondary outcomes include pain, performance-based and self-reported physical function and sarcopenia status. The success of this study will provide scientific evidence of whether the relatively cheap and well-tolerated vitamin D supplement can improve quadriceps muscle strength, physical function, pain symptoms, and sarcopenia status of this increasingly large population for end-stage knee OA patients. The study has great clinical significance given Hong Kong's lengthy and growing waiting list for complete knee replacement procedures. Trial registration: The trial was registered on clinicaltrials.gov (NCT05981534) on 31st July 2023.

Effect of lower-limb isokinetic muscle strengthening on knee function and joint contact force in knee osteoarthritis patients awaiting total knee arthroplasty: study protocol for a randomized controlled trial.

Knee osteoarthritis (OA) is a common and serious joint disease and patients mainly suffer from knee pain and dysfunction, significantly impacting their quality of life and daily activities. Non-pharmacological treatments and total knee arthroplasty (TKA) are the two major treatments for knee OA. TKA is the primary treatment for severe knee OA patients, however, the postoperative rehabilitation results are not entirely satisfactory. To enhance postoperative rehabilitation outcomes, preoperative lower-limb muscle strengthening has aroused attention and demonstrated significant results on functional recovery after TKA. Specifically, isokinetic muscle strengthening (IMS) has been highly anticipated as an efficient training method. Nevertheless, its effects in perioperative and long-term periods of TKA require further investigation. This study aims to evaluate the impact of preoperative lower-limb IMS during the 4weeks before TKA on the perioperative and postoperative outcomes, with particular attention on knee function, pain, and inflammatory response. In this study, 104 patients awaiting TKA will be randomized to 2 groups: the IMS and health education groups. All patients will be evaluated at baseline, post-intervention, discharge day, and postoperative day 14, with follow-up assessments at 6weeks, 3, 6, and 12months after discharge. The primary outcome will be the Knee Injury and Osteoarthritis Outcome Score 3months after TKA and the medial-to-lateral knee contact force ratio. The secondary outcomes will be changes in lower-limb muscle strength, knee pain, inflammation response, active range of motion, performance-based function (5-times Sit-to-Stand Test, Time Up-and-Go Test, 3m walking speed), Berg Balance Scale, and surgical need. Lower-limb IMS can improve muscle strength, pain, and function for early knee OA patients. However, the effects of different doses of IMS on perioperative and postoperative knee pain, inflammation response, and function after TKA are inconclusive. This study will provide high-quality evidence to assess the efficacy of IMS in end-stage patients who will undergo TKA. Understanding IMS in end-stage knee OA patients will help guide future surgical management for this population. Trial Registration Chinese Clinical Trial Registry ChiCTR2400088136.

Utilising Adaptive Choice-Based Conjoint Approach to Facilitate Shared Decision-Making in Osteoarthritis Management: A Patient Perception Study.

This study examines the application of the adaptive choice-based conjoint (ACBC) method to facilitate the shared decision-making (SDM) process for osteoarthritis (OA) treatment. The study recruited adult OA patients attending the rheumatology/orthopaedics clinics in a local urban hospital in Abu Dhabi, United Arab Emirates (UAE). Participants completed a questionnaire regarding who influences their decision in selecting OA medication, followed by an ACBC questionnaire about OA medication preferences and a questionnaire about the potential contribution of ACBC to the SDM process. A univariate analysis was used to investigate the relationships between participant variables and factors that influence their decision-making processes. The chi-squared, Fisher's exact, Cramer's V coefficient test and multivariable logistic regression analysis were utilised. The primary outcome investigates the contribution of the ACBC method to the SDM process for OA treatment. Secondary outcomes measure the association between patient demographics and variables related to the SDM process and ACBC questionnaire. Five hundred patients participated in this study, with a response rate (RR) of 100%. Most study participants were 60-69 years old (34.8%), females (78.8%), and UAE nationals (90.4%). Patients' opinions and online/paper information influencing their decision in selecting OA medication had a statistically significant association with age, gender, education, and employment (P=0.001 - 0.039). Employment status showed the strongest association (φc=0.170) with being independent in making the decision about OA medications, while education levels showed the strongest association (φc=0.24) with decisions impacted by online/paper information. The results of the multivariable logistic analysis showed that the only statistically significant variable for online/paper information that influenced the decision in selecting OA medication was education level (p=0.003). Most participants agreed or strongly agreed that the ACBC predicted their preferences for OA treatment (96.8%), the questionnaire may help doctors understand patients' preferences (93%) and recommended the use of ACBC tool doctors' clinics to aid the SDM process (92.8%) between patients and their physicians. ACBC approach can facilitate doctors' understanding of patients' preferences and aid the SDM process. Most OA patients are independent or influenced by their physician when making decisions about OA medication. Higher education and employment among OA patients are associated with a better involvement in the SDM process for available treatment.

Cardiovascular health metrics and all-cause mortality in osteoarthritis, inflammatory arthritis, and unclassified arthritis patients: a national prospective cohort study

BackgroundArthritis notably elevates mortality risk. It remains unclear whether the cardiovascular health (CVH) metrics improves the risk of all-cause mortality in patients with all types of arthritis.MethodsThis study data from the National Health and Nutrition Examination Survey to probe the link between CVH and all-cause mortality among arthritis sufferers in the United States. CVH evaluation employed the Life's Essential 8 metrics. Mortality outcomes were scrutinized using Cox proportional hazard regression models. Additionally, a restricted cubic spline analysis delineated the linear relationship between CVH and mortality. The study also delved into the singular impact of each CVH component on mortality.ResultsIn the cohort of 5919 patients with arthritis, improved CVH was linked to lower all-cause mortality. Specifically, each 10-point increment in CVH score was associated with a substantial decline in all-cause mortality risk [unadjusted hazard ratio (HR): 0.77, 95% Confidence Interval (95% CI): 0.71–0.83, P < 0.001]. Adjustments for age, sex, race, and social determinants of health further refined the HR to 0.72 (95% CI: 0.67–0.79, P < 0.001). Higher versus lower CVH scores at baseline markedly reduced mortality risk, with the most substantial decrease seen in those with ideal CVH metrics (HR: 0.39, 95% CI: 0.26–0.59, P < 0.001). Similar results were not observed in patients with inflammatory arthritis, but were seen in those with osteoarthritis or degenerative arthritis, and unknown types of arthritis.ConclusionIdeal CVH substantially decreases all-cause mortality risk among patients with arthritis, confirming the critical role of CVH in arthritis management. This study advocates for CVH interventions as part of comprehensive arthritis treatment plans.

Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.

Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) scores can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who are middle-aged and older remains unknown. This retrospective cohort study included 3566 individuals from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, and cardiovascular disease were conducted. After the follow-up was terminated, 920 participants experienced all-cause mortality, and 2646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality (hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.83-0.95). The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR = 1.46, 95% CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups. This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.

The Effect of TENS and Ultrasound Diathermy on Osteoarthritis Patients in Physical Medicine and Rehabilitation Unit of Patut Patuh Patju Hospital, West Nusa Tenggara

Osteoarthritis is generally recognized as a common musculoskeletal condition in Indonesia, characterized by the degeneration of joint cartilage and narrowing of the joint space. The form of therapy that can be given to knee OA patients is a combination of TENS therapy and ultrasound diathermy (USD). WOMAC is an index used to measure osteoarthritis patiens based on pain, stiffness, and physical function. Patut Patuh Patju General Hospital is the only hospital in West Lombok district where physical medicine and medical rehabilitation have recently been introduced. This research aims to determine the effects of administering TENS and ultra sound diathermy on OA patients in the physical medicine and rehabilitation unit of Patut Patuh Patju Hospital, a newly established district hospital in NTB, which has been operational for the past year. This type of research uses a pre-experimental design with a one group pretest-posttest method. Sampling was taken using a purposive sampling technique with a total sample of 30. The research population was knee osteoartritis patients undergoing physiotherapy treatment at the Medical Rehabilitation Unit of Patut Patuh Patju General Hospital. Data was collected using the WOMAC questionnaire before and after 6 until 8 times therapy. The distribution of research data was analyzed using the Shapiro-Wilk test. If the data distribution is normal, it is analyzed using the paired t-test, whereas if it is not normal, it is analyzed using the Wilcoxon test. The combination of TENS therapy and ultra sound diathermy results in improvement of WOMAC scores in knee osteoarthritis patients with p-value = 0.000 (p &lt; 0.05).

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.

Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2

M1 polarization of synovial macrophages contributes to cartilage degeneration and osteoarthritis (OA) development. However, limited knowledge is available about how M1 macrophages affect the biological properties of chondrocytes. This study aimed to explore the role of exosomal microRNAs (miRs) released from M1 macrophages in modulating the proliferation and survival of chondrocytes. Through bioinformatic analysis and experimental validation, we indicated that miR-363 was selectively induced in M1 macrophages (CD68+CD80+) but not M2 macrophages (CD68+CD206+). The upregulation of miR-363 in M1 macrophages depended on the activation of STAT1 signaling. Clinically, OA patients had a significantly higher miR-363 level in synovial fluid than control individuals without OA. Functional studies revealed that inhibition of miR-363 blocked the M1 macrophage polarization induced by lipopolysaccharide and IFN-γ. Moreover, exosomal miR-363 released from M1 macrophages significantly suppressed the proliferation and survival and induced inflammatory gene expression in chondrocytes. G3BP2 was identified as a target gene for miR-363 and could be negatively regulated by miR-363. Knockdown of G3BP2 recapitulated the effect of miR-363 overexpression on chondrocytes. Most importantly, enforced expression of G3BP2 attenuated miR-363-induced apoptosis and inflammatory response in chondrocytes. In conclusion, miR-363 plays an indispensable role in M1 macrophage polarization and can be released from M1 macrophages via exosomes to cause chondrocyte injury and inflammation. The miR-363/G3BP2 axis may represent a promising target for the prevention of OA development.

Can individual functional improvements be predicted in osteoarthritic patients after total knee arthroplasty?

PurposeTotal knee arthroplasty (TKA) is an effective treatment for advanced osteoarthritis, and achieving optimal outcomes can be challenging due to various influencing factors. Previous research has focused on identifying factors that affect postoperative functional outcomes. However, there is a paucity of studies predicting individual postoperative improvement following TKA. Therefore, a quantitative prediction model for individual patient outcomes is necessary.Materials and methodsDemographic data, radiologic variables, intraoperative variables, and physical examination findings were collected from 976 patients undergoing TKA. Preoperative and 1-year postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were assessed, and multivariate regression analysis was conducted to identify significant factors influencing one-year WOMAC scores and changes in WOMAC scores. A predictive model was developed on the basis of the findings.ResultsThe predictive accuracy of the model for 1-year WOMAC scores was poor (all adjusted R2 < 0.08), whereas the model for changes in WOMAC scores demonstrated strong predictability (all adjusted R2 > 0.75). Preoperative WOMAC scores, sex, and postoperative knee range of motion significantly affected all pain, stiffness, and physical function aspects of the WOMAC scores (all P < 0.05). Age, cerebrovascular disease, and patellar resurfacing were associated with changes in physical function (all P < 0.05).ConclusionsThe developed quantitative model demonstrated high accuracy in predicting changes in WOMAC scores after TKA. The identified factors influencing postoperative improvement in WOMAC scores can assist in optimizing patient outcomes after TKA.

Modulation of Carnitine Palmitoyl Transferase 1b Expression and Activity in Muscle Pathophysiology in Osteoarthritis and Osteoporosis

In the pathophysiology of osteoarthritis and osteoporosis, articular cartilage and bone represent the target tissues, respectively, but muscle is also involved. Since many changes in energy metabolism occur in muscle with aging, the aim of the present work was to investigate the involvement of carnitine palmitoyl transferase 1b (Cpt1b) in the muscle pathophysiology of the two diseases. Healthy subjects (CTR, n = 5), osteoarthritic (OA, n = 10), and osteoporotic (OP, n = 10) patients were enrolled. Gene expression analysis conducted on muscle and myoblasts showed up-regulation of CPT1B in OA patients; this result was confirmed by immunohistochemical and immunofluorescence analyses and enzyme activity assay, which showed increased Cpt1b activity in OA muscle. In addition, CPT1B expression resulted down-regulated in cultured OP myoblasts. Given the potential involvement of Cpt1b in the modulation of oxidative stress, we investigated ROS levels, which were found to be lower in OA myoblasts, and gene expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (Nox4), which resulted up-regulated in OA cells. Finally, the immunofluorescence of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) showed a decreased expression in OP myoblasts, with respect to CTR and OA. Contextually, through an ultrastructural analysis conducted by Transmission Electron Microscopy (TEM), the presence of aberrant mitochondria was observed in OP muscle. This study highlights the potential role of Cpt1b in the regulation of muscle homeostasis in both osteoarthritis and osteoporosis, allowing for the expansion of the current knowledge of what are the molecular biological pathways involved in the regulation of muscle physiology in both diseases.

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.