Efficiently directing differentiation and homing of mesenchymal stem cells to boost cartilage repair in osteoarthritis via a nanoparticle and peptide dual-engineering strategy.

Mesenchymal stem cells (MSCs) are expected to be useful therapeutics in osteoarthritis (OA), the most common joint disorder characterized by cartilage degradation. However, evidence is limited with regard to cartilage repair in clinical trials because of the uncontrolled differentiation and weak cartilage-targeting ability of MSCs after injection. To overcome these drawbacks, here we synthesized CuO@MSN nanoparticles (NPs) to deliver Sox9 plasmid DNA (favoring chondrogenesis) and recombinant protein Bmp7 (inhibiting hypertrophy). After taking up CuO@MSN/Sox9/Bmp7 (CSB NPs), the expressions of chondrogenic markers were enhanced while hypertrophic markers were decreased in response to these CSB-engineered MSCs. Moreover, a cartilage-targeted peptide (designated as peptide W) was conjugated onto the surface of MSCs via a click chemistry reaction, thereby prolonging the residence time of MSCs in both the knee joint cavity of mice and human-derived cartilage. In a surgery-induced OA mouse model, the NP and peptide dual-modified W-CSB-MSCs showed an enhancing therapeutic effect on cartilage repair in knee joints compared with other engineered MSCs after intra-articular injection. Most importantly, W-CSB-MSCs accelerated cartilage regeneration in damaged cartilage explants derived from OA patients. Thus, this new peptide and NPs dual engineering strategy shows potential for clinical applications to boost cartilage repair in OA using MSC therapy.

The common link between sleep apnea syndrome and osteoarthritis: a literature review.

Patients with Osteoarthritis (OA) often also suffer from Sleep Apnea Syndrome (SAS), and many scholars have started to notice this link, although the relationship between the two is still unclear. In this review, we aim to summarize the current literature on these two diseases, integrate evidence of the OA and OSA connection, explore and discuss their potential common mechanisms, and thus identify effective treatment methods for patients with both OA and SAS. Some shared characteristics of the two conditions have been identified, notably aging and obesity as mutual risk factors. Both diseases are associated with various biological processes or molecular pathways, including mitochondrial dysfunction, reactive oxygen species production, the NF-kB pathway, HIF, IL-6, and IL-8. SAS serves as a risk factor for OA, and conversely, OA may influence the progression of SAS. The effects of OA on SAS are underreported in the literature and require more investigation. To effectively manage these patients, timely intervention for SAS is necessary while treating OA, with weight reduction being a primary requirement, alongside combined treatments such as Continuous positive airway pressure (CPAP) and medications. Additionally, numerous studies in drug development are now aimed at inhibiting or clearing certain molecular pathways, including ROS, NF-KB, IL-6, and IL-8. Improving mitochondrial function might represent a viable new strategy, with further research into mitochondrial updates or transplants being essential.

Association between osteoarthritis with Parkinson's disease in the US (NHANES 2011-2020).

Objected: To evaluate the association between osteoarthritis (OA) and Parkinson's disease (PD) in adults in the United States. Methods: Using 2011-2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI. Results: In this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p < 0.001). After adjusting the covariates, the results are still stable. Conclusion: PD patients were positively correlated with OA. Among people with OA, there was a 95% increased risk of PD compared to people without arthritis. Therefore, when treating OA, attention should be paid to the increased risk of PD. In the meantime, further studies are needed to explore the link between OA and PD patients.

Altered activation patterns of the sensory-motor cortex in patients with knee osteoarthritis during knee isokinetic movement at different speeds.

Background: Abnormal brain activation patterns in patients with knee osteoarthritis (KOA) at rest have been revealed, but it is unclear how brain activation patterns change during movement. This study aimed to investigate the alterations in brain activation patterns in KOA patients during knee isokinetic movement, and the correlation between cortical activity changes and pain severity and dysfunction. Methods: Eighteen patients with KOA and 18 healthy controls (HC) were recruited, and to performed the knee isokinetic test with three speeds. Functional near-infrared spectroscopy (fNIRS) was used to detect the cerebral cortex hemodynamics changes of primary somatosensory (S1), primary motor (M1) and somatosensory association cortex (SAC) in the region of interest (ROI) during movement. Then, we evaluated potential correlations between M1, S1 and SAC values and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores. Results: The results showed that peak torque of knee extension in KOA patients was significantly smaller than that in HC. For HC, unilateral knee movement activated bilateral ROIs. The contralateral activation was dominant, showing the phenomenon of high contralateral activation. For KOA patients, there were no statistical difference in the activation level between the left and right of the cerebral cortex, with both sides showing lower activation levels compared to HC. Further analysis found that the contralateral M1, S1, and SAC of the affected knee in KOA patients were significantly lower than those in HC, while no difference was found on the ipsilateral side. Moreover, during isokinetic movement at 180°/s, VAS score in KOA patients was negatively correlated with the activation level of the contralateral S1 and M1 values, and WOMAC was negatively correlated with the activation level of the contralateral M1 value. Conclusion: Contralateral activation of the sensorimotor cortex exists during unilateral knee movement, but in KOA patients, this contralateral cortical activation is suppressed. Furthermore, the clinical pain and dysfunction in KOA patients are associated with activation levels of specific brain regions. These findings can provide a better understanding of KOA brain science and are expected to contribute to the development of central intervention for the disease.

Modified volar approach for proximal row carpectomy.

Objectives: Proximal row carpectomy is a well-accepted surgical procedure for the management of traumatic and degenerative wrist pathologies. It is routinely performed through a dorsal approach; a volar surgical access was presented in order to enable concomitant carpal tunnel release and avoid flexion limitation or disabilities caused by adhesions of the dorsal capsule and extensor tendons. We propose a modification to the volar approach, with detailed description of skin incision (reproducing the standard palmar access to the scaphoid), capsular section (beginning with a longitudinal cut radial to flexor carpi radialis tendon and prolonged transversally along the radio-lunate joint) and sequence of carpal bone removal (starting with the scaphoid rather than the lunate). Materials and methods: The patients who underwent surgical treatment with modified volar proximal row carpectomy between 1992 and 2015 were enrolled in a retrospective analysis. Results: We report postoperative improvement in both the Mayo Wrist score and total active range of motion in 38 patients, in line with the outcomes of dorsal proximal row carpectomy. Conclusions: The modified volar approach is highly recommended when better visualization and access to proximal carpal bones are needed (particularly useful for inveterate perilunate dislocations), moreover if concomitant carpal tunnel syndrome or extensor tendon pathologies are present.

Investigating the relationship between radiographic joint space width loss and deep learning-derived magnetic resonance imaging-based cartilage thickness loss in the medial weight-bearing region of the tibiofemoral joint.

Objective: To investigate the relationship between measures of radiographic joint space width (JSW) loss and magnetic resonance imaging (MRI)-based cartilage thickness loss in the medial weight-bearing region of the tibiofemoral joint over 12-24 months. To stratify this relationship by clinically meaningful subgroups (sex and pain status). Design: We analyzed a subset of knees (n â€‹= â€‹256) from the Osteoarthritis Initiative (OAI) likely in early stage OA based on joint space narrowing (JSN) measurements. Natural logarithm transformation was used to approximate near normal distributions for JSW loss. Pearson Correlation coefficients described the relationship between ln-transformed JSW loss and several versions of deep learning-derived MRI-based cartilage thickness loss parameters (minimum, maximum, and mean) in subregions of the femoral condyle, tibial plateau, and combined femoral and tibial regions. Linear mixed-effects models evaluated the associations between the ln-transformed radiographic and MRI-derived measures including potential confounders. Results: We found weak correlations between ln-transformed JSW loss and MRI-based cartilage thickness ranging from R â€‹= â€‹-0.13 (p â€‹= â€‹0.20) to R â€‹= â€‹0.26 (p â€‹< â€‹0.01). Correlations were higher (still poor) among females compared to males and painful compared to non-painful knees. Model results showed weak associations for nearly all MRI-based measures, ranging from no association to ß (95% CI) â€‹= â€‹0.25 (0.11, 0.39). Associations were higher among females compared to males and minimal differences between painful and non-painful knees. Conclusions: Despite its recommended use in disease-modifying OA drug clinical trials, results suggest that JSW loss is an ineffective proxy measure of cartilage thickness loss over 12-24 months and within a localized region of the tibiofemoral joint.

A systematic review on Autologous Matrix Induced Chondrogenesis (AMIC) for chondral knee defects.

BACKGROUND: Chondral defects of the knee can be identified in up to 60% of patients undergoing knee arthroscopy. The use of Autologous Matrix Induced Chondrogenesis (AMIC), which combines subchondral microfracture with a collagen membrane,has been increasingly used to treat these defects. AIMS: This review assesses the clinical, functional, and radiological outcomes of patients undergoing the AMIC procedure and reports any associated complications. METHODS: Studies with a minimum of 10 patients and fulfilled at least a 12-month follow up period with more than 70% follow up rate were included. Methodological quality was assessed using MINORS (Methodological Index for Non-Randomised Studies) criteria. The meta-analysis compared Lysholm, VAS (Visual Analog Scale), IKDC (International Knee Documentation Committee), KOOS (Knee Injury and Osteoarthritis Outcome Score) Pain, and Tegner clinical outcome measures at baseline and follow up. RESULTS: 18 studies (n = 490 patients) were included. The mean age was 35.2 [SD = 5.0] years and the mean defect size was 3.47 [SD = 0.96] cm2. There was a clinically significant improvement in Lysholm, IKDC, and KOOS scores of 30.36 [95% CI (25.80, 34.93)], 34.05 [95% CI (4.16, 43.95)], and 30.63 [95% CI (24.78, 36.47)] respectively; and reduction in VAS pain score of -4.10 [95%CI (-4.50, -3.71) at follow up. Improvement in Tegner score at follow up was not statistically significant: 0.21 [95% CI (-0.88, 1.30)],(p > 0.05). CONCLUSION: AMIC is a safe, effective, and reliable technique to treat knee chondral defects which can provide significant clinical, functional, and radiological improvements to patients.

The association between anxiety and depression symptoms and clinical and pain characteristics in patients with hip and knee osteoarthritis.

OBJECTIVES: This study aimed to estimate the prevalence of anxiety and depression symptoms and explore the association between these symptoms and clinical and pain characteristics in patients with chronic pain (CP) due to hip and knee osteoarthritis (OA). METHODS: In this cross-sectional study, adult patients with CP and knee and/or hip OA were included. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Visual analogue scale, Western Ontario and McMaster Universities Arthritis Index (WOMAC) and PainDetect Questionnaire assessed pain characteristics and Health Assessment Questionnaire (HAQ) evaluated functional disability. Correlation coefficients were used to explore the associations between anxiety and depression symptoms and clinical and pain characteristics. RESULTS: A total of 61 patients (age 66.2±9.4 years, 67.2% female) were included. Most patients (70.5%) had clinically significant anxiety and/or depression symptoms. Patients with anxiety and/or depression symptoms had higher pain severity (p=0.032) and disability (p=0.014). Depression symptoms had a moderate positive correlation with WOMAC physical function subscale (r=0.520), WOMAC total (r=0.511) and HAQ (r=0.405). CONCLUSIONS: Anxiety and depression symptoms are prevalent in knee or hip OA patients with CP and were associated with higher pain severity and functional disability. These findings support the screening of anxiety and depression symptoms in OA patients, in order to develop more effective multidisciplinary treatments.

The cereblon-AMPK (AMP-activated protein kinase) axis in chondrocytes regulates the pathogenesis of osteoarthritis.

OBJECTIVE: AMP-activated protein kinase (AMPK) dysregulation is implicated in osteoarthritis (OA), but the mechanisms underlying this dysregulation remain unclear. We investigated the role of cereblon, a substrate-recognition protein within the E3-ligase ubiquitin complex, in AMPK dysregulation and OA pathogenesis. METHODS: Cereblon expression was examined in human (n = 5) and mouse (n = 10) OA cartilage. The role of cereblon was investigated through its adenoviral overexpression (n = 10) or knockout (KO, n = 15) in the destabilization of the medial meniscus (DMM)-operated mice. The therapeutic potentials of the chemical cereblon degrader, TD-165, and the AMPK activator, metformin, were assessed through intra-articular (IA) injection to mice (n = 15). RESULTS: Immunostaining revealed that cereblon is upregulated in human and mouse OA cartilage. In DMM model mice, cartilage destruction was exacerbated by overexpression of cereblon in mouse joint tissues (OARSI grade; 1.11 [95% CI: 0.50 to 2.75]), but inhibited in global (-2.50 [95% CI: -3.00 to -1.17]) and chondrocyte-specific (-2.17 [95% CI: -3.14 to -1.06]) cereblon KO mice. The inhibitory effects were more pronounced in mice fed a high-fat diet compared to a regular diet. The degradation of cereblon through IA injection of TD-165 inhibited OA cartilage destruction (-2.47 [95% CI: -3.22 to -1.56]). Mechanistically, cereblon exerts its catabolic effects by negatively modulating AMPK activity within chondrocytes. Consistently, activation of AMPK by IA injection of metformin inhibited posttraumatic OA cartilage destruction (-1.20 ([95% CI: -1.89 to -0.45]). CONCLUSIONS: The cereblon-AMPK axis acts as a catabolic regulator of OA pathogenesis and seems to be a promising therapeutic target in animal models of OA.

Systematic review and meta-analysis of long term outcomes and innovations in Total Knee Arthroplasty: KINEMATIC, PERSONALIZED KNEE vs. CONVENTIONAL.

Background: Kinematic alignment is an emerging approach for total knee arthroplasty, with the aim to restore patient's individual pre-arthritic joint kinematics. In this systematic review and meta-analysis, we compared the kinematic alignment with the conventional mechanical alignment for total knee arthroplasty. Methods: We searched PubMed, Web of Science, Cochrane Library, and Scopus on June 2, 2024. We screened the retrieved studies for eligibility. Then extracted the data from the included studies, and then pooled the data as mean difference (MD) or odds ratio (OR) with a 95% confidence interval using Review Manager Software (ver. 3.5). Results: There was no significant difference between KA and MA in the different reported scores: combined KSS score at 6 months (P = 0.23) and 1 years (P = 0.60), KSS Patient satisfaction (P = 0.33), KSS function score (P = 0.07), Oxford score at 6 months (P = 0.45) and 2 years (P = 0.41), KOOS score (P = 0.26). Moreover, there was statistically significant difference in range of motion for flexion and extension at 1 and 2 years, incision length, the length of hospital stay, or the duration of surgery. Conclusion: Although kinematic alignment showed slightly better clinical outcomes than mechanical alignment, the difference between the two techniques is not statistically significant.

tRNA-derived fragment 3031B regulates human anterior cruciate ligament cell proliferation and survival by targeting RELA.

tRNA-derived fragments (tRFs) are novel short noncoding RNAs that play pivotal roles in cell proliferation and survival. However, knowledge of the biological roles of tRFs in anterior cruciate ligament (ACL) cells is limited. Here, we intended to investigate the function of tRF-3031B in ACL cell. We used the tRF and tiRNA array to analyze tRF and tiRNA expression profiles in osteoarthritis (OA) ACL cells and normal ACL cells, and qRT-PCR and fluorescence in situ hybridization (FISH) were used to determine tRF-3031B expression. The results showed that tRF-3031B was expressed at low levels in OA ACL and Interleukin-1ß (IL-1ß) treated ACL cells. We found that RELA was the target of tRF-3031B. When ACL cells were transfected with tRF-3031B mimics, RELA expression was suppressed, whereas transfection with tRF-3031B inhibitors had the opposite effect. The rescue and dual-luciferase reporter assays showed that tRF-3031B silenced the RELA expression by binding to its untranslated region (3'-UTR). Hence, this study showed the novel function of tRF-3031B in regulating ACL cell proliferation and survival by targeting RELA, and these findings may offer a new direction for the study of ACL degeneration and pathophysiological of OA.

Comparative study on the association between types of physical activity, physical activity levels, and the incidence of osteoarthritis in adults: the NHANES 2007-2020.

It is known that physical activity is beneficial for the prevention of osteoarthritis (OA), but specific discussions on which types and levels of physical activity are more effective in reducing the incidence of OA are restricted. This study is aimed at exploring the correlation concerning the types of physical activity, levels of physical activity, and the incidence of OA by assessing the participation in five typical forms of physical activity (vigorous work activity, vigorous recreational activity, moderate work activity, moderate recreational activity, and walking or bicycling). Cross-sectional study was conducted. Self-reported data on specific types of physical activity were obtained from individuals in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020 with the use of the Physical Activity Questionnaire (PAQ). The incidence of OA was assessed through the "Health Conditions" questionnaire section of NHANES. Weighted logistic regression analysis was employed to study the correlation between physical activity types and levels, and the incidence of OA. Different kinds of physical activity and physical activity levels have varying impacts on the incidence of OA. Among the types of physical activity, vigorous recreational activity and moderate recreational activity are found to have a preventive effect on OA. In terms of physical activity levels, low physical activity levels of moderate work activity are associated with an increased risk of OA, while moderate physical activity levels are confirmed to have a protective effect against OA in the age groups of 20-44 and 45-64. However, gender-stratified analyses reveal that both low and moderate physical activity levels provide protection against OA in males, with moderate physical activity levels showing a more significant protective effect.

Left Infrapatellar Branch of the Saphenous Peripheral Nerve Stimulation Relieves Refractory Pain Following Total Knee Replacement.

Osteoarthritis, the most common joint disease of adults worldwide, is increasing in prevalence due to an increase in aging and rates of obesity in developed countries. Treatment options include physical therapy, pharmacologic management, non-pharmacologic management, and total knee replacement surgery. When conservative measures fail, total knee replacement surgery is pursued. The patient is a 61-year-old woman with a history of severe chronic osteoarthritic knee pain following total left and right knee arthroplasty in 2016 and 2019, respectively, who presents with refractory post-total knee replacement pain. Following her surgeries, the patient was in excruciating 10/10 pain on the numerical rating scale (NRS) and was unable to walk or stand. She underwent revisions which, unfortunately, did not ameliorate her pain. She was later referred to chronic pain management in which a peripheral nerve stimulator (PNS) was offered and implanted. Following her PNS trial, the patient achieved >80% pain relief in her left knee. After the permanent PNS implant, the patient noted she had 100% pain relief (0/10 on the NRS) in her left knee and was able to regain mobility. Here, we discuss a case demonstrating rapid pain relief following the minimally invasive PNS implantation for refractory pain following total knee arthroplasty. Refractory pain following total knee arthroplasty can increase morbidity and mortality as a consequence. Thus, proper management is needed to reduce these adverse outcomes. In patients who have failed conservative medical management, PNS may be an alternative, efficacious treatment option for refractory knee pain. Despite the efficacy in our case, further research is needed to define the optimal patient group that would benefit from PNS for refractory knee pain following total knee arthroplasty.

Total Knee Arthroplasty With Long-Stem Implant: A Case Report of a Patient With Extreme Varus Deformity.

Constrained implants have become more common in difficult primary total knee arthroplasty (TKA) cases in recent years because they may more effectively and conveniently handle the substantial instability that is evident in osteoarthritis of knees with severe varus deformity. However, the need for a constrained TKA in such conditions is controversial, as constraint implants come with a bargain of stability for longitivity. In this case report, we have successfully shown that even in cases of significant instability and bone loss, intraoperative conversion to a restricted device is rarely necessary. In our case report, a 83-year-old female had complaints of severe pain in bilateral knees, with the right knee more than the left knee, since 12 years with severe varus deformity in the right knee. Physical examination revealed swelling and medial joint line tenderness with restriction of range of motion in bilateral knees. Pre-anesthetic checkup of the patient was done and patient was given clearance for surgery under American Society of Anesthesiologist (ASA)-2, total knee arthroplasty with a long stem was done, extreme varus deformity was corrected, osteophytes removed and tibial bone loss was repaired with bone cement. Post operatively patient showed significant improvement and McMaster University and Western Ontario Osteoarthritis Index (WOMAC) and Knee Society Scores (KSS) for pain, stiffness, and physical function during everyday activities were significantly improved compared to pre-operative assessment.

Multiple applications of metal-organic frameworks (MOFs) in the treatment of orthopedic diseases.

Pharmacologic treatment of orthopedic diseases is a common challenge for clinical orthopedic surgeons, and as an important step in the stepwise treatment of orthopedic diseases, it is often difficult to achieve satisfactory results with existing pharmacologic treatments. Therefore, it is increasingly important to find new ways to effectively improve the treatment pattern of orthopedic diseases as well as to enhance the therapeutic efficacy. It has been found that metal-organic frameworks (MOFs) possess the advantages of high specific surface area, high porosity, chemical stability, tunability of structure and biocompatibility. Therefore, MOFs are expected to improve the conventional traditional treatment modality for bone diseases. This manuscript reviewed the applications of MOFs in the treatment of common clinical bone diseases and look forward to its future development.

Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses.

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by ß-cyclodextrin (ß-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-ß-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes.

Ginkgolide A enhances FoxO1 expression and reduces endoplasmic reticulum stress to mitigate osteoarthritis in mice.

This study aimed to investigate the effects of Ginkgolide A (GA) on chondrocytes under oxidative stress and to elucidate its potential molecular mechanisms. Using a destabilization of the medial meniscus (DMM) model in mice and an in vitro osteoarthritis (OA) model induced by tert-butyl hydroperoxide (TBHP) in chondrocytes, we validated the therapeutic efficacy and underlying mechanisms of GA. Potential OA targets of GA were identified through network pharmacology, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Further exploration into the effects on endoplasmic reticulum stress (ERS), apoptosis, extracellular matrix (ECM) degradation, and Forkhead Box O1 (FoxO1) related pathways was conducted using Western blotting, immunofluorescence, TUNEL staining, flow cytometry, X-ray, micro-computed tomography (Micro-CT) analysis, and histological staining. The results demonstrated that GA upregulated FoxO1 expression and inhibited ERS-related signaling pathways, thereby reducing apoptosis and ECM degradation. In conclusion, GA significantly alleviated OA symptoms both in vitro and in vivo, suggesting its potential as a therapeutic agent for OA.

Metabolic syndrome, radiographic osteoarthritis progression and chronic pain of the knee among men and women from the general population: The Rotterdam study.

OBJECTIVE: Although a relationship between osteoarthritis and components of metabolic syndrome (MetS) has been suggested, most of the results have been cross-sectional. We, therefore, aimed to investigate the sex-specific longitudinal association of (components of) MetS with progression of radiographic osteoarthritis and chronic pain in the knee joints in a large prospective cohort. METHOD: In the large population-based Rotterdam study of up to 6,138 individuals, median follow-up time 5.7 (IQR 5.5) years, we examined the relation between MetS and its components (abdominal obesity, high triglycerides, low high-density lipoprotein, elevated blood pressure, and type 2 diabetes) with the progression of osteoarthritis using generalized estimating equations, generalized linear models and competing risk analysis. Analyses were stratified for sex. Covariates adjusted for: age, smoking, alcohol use, education, sub-cohort, baseline K/L grade, months between radiographs and BMI. RESULTS: The presence of MetS (37.6 % in men, 39 % in women) and elevated blood pressure was associated with an increased risk of knee osteoarthritis progression in both men and women. MetS was associated with an increased risk of incident chronic knee pain (CKP) in men. In addition, abdominal obesity and high triglycerides showed higher riskfor incidence of CKP in men,but not in women. The associations were attenuated and no longer significant after BMI-adjustment, except for the association of MetS and high triglycerides with incidence of CKP in men that stayed significant (OR 1.04, 95 %CI 1.00-1.07 for MetS and OR 1.04, 95 %CI 1.01-1.07 for high triglycerides). CONCLUSION: Metabolic syndrome and individual metabolic components, such as abdominal obesity and elevated blood pressure, were associated with radiographic progression of knee OA in both men and women, but not independent of BMI. Metabolic syndrome and high triglycerides were associated with incidence of CKP only in men.

The Differences in Parameters in Ultrasound Imaging and Biomechanical Properties of the Quadriceps Femoris with Unilateral Knee Osteoarthritis in the Elderly: A Preliminary Observational Study.

Purpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.

Intra-articular injection of platinum nanozyme-loaded silk fibroin/pullulan hydrogels relieves osteoarthritis through ROS scavenging and ferroptosis suppression.

Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.