This study was designed to explore the biomechanical impacts of the proximal fibular osteotomy (PFO) on medial compartment knee osteoarthritis (KOA). Furthermore, this study utilized finite element analysis (FEA) to examine the biomechanical impacts of PFO on medial compartment KOA both pre- and post-surgery.

Fifteen individuals with medial compartment KOA were selected randomly. Three-dimensional reconstruction software, coupled with FEA software, was employed to model PFO, allowing observation of changes in stress distribution, peak stress, and contact area of articular cartilage in femoral cartilage, tibial plateau cartilage, and meniscus before and after PFO.

After PFO, significant changes in peak stress and stress distribution in the knee joint (KJ) were observed. The stress distribution shifts notably from the medial side to the lateral side. A significant reduction in peak values was observed in the medial femoral cartilage (changing from 1.91 ± 0.44 to 1.40 ± 0.14), medial meniscus (2.89 ± 0.72 to 2.05 ± 0.49), and medial tibial plateau cartilage (2.25 ± 0.65 to 1.60 ± 0.38). On the contrary, an increase in these metrics was recorded in the lateral femoral cartilage (changing from 1.10 ± 0.32 to 1.59 ± 0.30), lateral meniscus (1.82 ± 0.58 to 2.49 ± 0.60), and lateral tibial plateau cartilage (0.95 ± 0.21 to 1.40 ± 0.26). In addition, the stress distribution area of articular cartilage was reduced significantly in the medial dimension (346.25 ± 55.66 to 267.05 ± 51.05) and increased in the lateral dimension (219.35 ± 38.89 to 333.25 ± 29.90).

PFO demonstrates effectiveness in alleviating stress within the medial compartment of the KJ, presenting a straightforward and efficacious approach for managing medial compartment KOA.

In this study, we developed an intra-articular injectable hydrogel drug depot (SMN-CeO2@G) for sustained OA treatment. This hydrogel system, which carries sinomenine-loaded cerium dioxide nanoparticles (SMN-CeO2), enhances anti-inflammatory and anti-apoptotic effects within the joint cavity. SMN-CeO2@G features a three-dimensional network structure with an approximate pore size of 10 μm, stably encapsulating SMN-CeO2 nanoparticles (∼75 nm). Under hydrogen peroxide (H2O2) exposure and simulated mechanical stress, SMN-CeO2@G achieves a cumulative SMN release of 44.72 ± 7.83% over 48 hours, demonstrating controlled release capabilities. At an SMN concentration of 0.5 μg/mL, SMN-CeO2@G significantly enhances proliferation, reduces apoptosis, and lowers matrix metalloproteinases-13 (MMP-13) secretion in IL-1β-induced ATDC5 chondrocytes. In the ATDC5-RAW264.7 co-culture model, SMN-CeO2@G effectively reduces reactive oxygen species (ROS) levels, apoptosis (∼20%), and MMP13 concentrations (24.3 ± 3.1 ng/mL) in chondrocytes, likely due to the promotion of macrophages M2 polarisation. In anti-OA efficacy studies, a single intra-articular injection of SMN-CeO2@G significantly reduces osteophyte formation, promotes subchondral bone normalisation, alleviates pain sensitivity, and lowers serum IL-1β (59.3 ± 2.4 pg/mL) and MMP-13 (23.6 ± 1.7 ng/mL) levels in OA model rats. SMN-CeO2@G also achieves prolonged retention in the synovial fluid, with 6.7 ± 2.8% SMN still detectable at 72 hours post-injection, a factor crucial for sustained therapeutic effect. Overall, SMN-CeO2@G presents a promising tool for intra-articular OA treatment.

Small extracellular vesicles (sEVs) are considered promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study aimed to explore the molecular mechanism by which M2 macrophage-derived sEVs (M2-sEVs) modulate chondrocyte proliferation and apoptosis, thereby affecting OA progression. M2 macrophages were successfully induced, and M2-sEVs were successfully isolated. The sEVs were small vesicles with diameters ranging from 50 to 150 nm. The exosomal markers, including CD9, CD63, and CD81, were highly expressed, whereas the negative marker calnexin was absent in M2-sEVs. M2-sEVs effectively alleviated OA tissue and chondrocyte damage in both in vivo and in vitro models, evidenced by reduced rat knee joint injury, increased chondrocyte viability, and decreased chondrocyte apoptosis and extracellular matrix (ECM) degradation. Furthermore, M2-sEVs decreased the levels of pro-inflammatory cytokines IL-6 and TNF-α. Osteopontin (OPN) was upregulated within rats with OA and IL-1β-induced chondrocytes. Silencing of OPN exacerbated IL-1β-induced chondrocyte damage and partially abrogated the therapeutic effects of M2-sEVs. Additionally, M2-sEVs enhanced OPN expression and activated CD44 and the PI3K/AKT signaling pathway. In conclusion, M2-sEVs promoted OPN expression to improve knee joint tissue damage in rats with OA and chondrocyte damage. This protective effect of M2-sEVs might be associated with the activation of CD44 and the PI3K/AKT signaling.

Histone lactylation is a novel epigenetic regulator that is reported to participate in gene expression. Ferroptosis is an oxidative form of cell death and chondrocyte ferroptosis crucially impacts the development of osteoarthritis (OA). The study aimed at investigating the effect of lactate dehydrogenase B (LDHB) and its mediated histone lactylation on chondrocyte ferroptosis during OA.

Our study focused on the establishment of in vivo mouse model and in vitro interleukin-1β (IL-1β)-induced chondrocytes model and administrated LDHB knockdown (siLDHB). Histopathological assessment of cartilage was conducted via HE staining, while serum levels of cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptides of type II collagen (CTX-II) were quantified using ELISA to evaluate OA severity. The matrix degradation was further examined by expression of Collagen II and Aggrecan. Levels of total iron, ferrous iron (Fe2+), and lipid reactive oxygen species (ROS) were considered measurements of ferroptosis. Assessment of cell viability and proliferation relied on cell counting kit 8 (CCK-8) together with colony formation assay. Western blotting assay served for detecting the relative expression of proteins and protein lactylation. The epigenetic regulation of ACSL4 by LDHB was determined by chromatin immunoprecipitation (ChIP) and luciferase reporter gene assay.

OA mice presented remarkably elevated protein level of LDHB and H3K18 lactylation in the cartilage versus the sham group. Knockdown of LDHB downregulated the levels of COMP and CTX-II, as well as alleviated chondrocyte ferroptosis in vitro and in vivo. Results from ChIP and luciferase reporter gene assay demonstrated direct histone lactylation of ACSL promoter, and knockdown of LDHB and treatment with LDH inhibitor reduced histone lactylation and expression of ACSL4. ACSL4 overexpression could reverse the impact of LDHB depletion on chondrocyte proliferation and ferroptosis.

LDHB promotes ACSL4 by histone lactylation to induce chondrocyte ferroptosis, which further contributes to OA development. The findings in the study assist in understanding the modulating mechanism of LDHB-mediated lactylation against chondrocyte ferroptosis in OA progression.

Total knee arthroplasty (TKA) can cause significant hidden blood loss after surgery, and transfusion or erythropoietin (EPO) treatment may be required. This study aimed to identify the factors associated with blood loss in patients undergoing TKA for osteoarthritis (OA).

We retrospectively enrolled 1444 OA patients undergoing primary TKA from January 2022 to June 2024. The patients were divided into two groups according to the grade of hidden blood loss. To identify the key influencing factors, we conducted a logistic regression analysis.

This study analyzed 1,444 primary arthroplasty cases, identifying 236 patients with high hidden blood loss (HHBL). Coronary artery disease (CAD) was significantly more prevalent in the HHBL group (15.3% vs. 9.4%, p = 0.006). Preoperative EPO use was higher in the low hidden blood loss (LHBL) group (21.9% vs. 9.3%, p < 0.001). Significant preoperative lab differences included hemoglobin, hematocrit, and platelet count. Surgical factors associated with HHBL included left knee TKA, conventional mechanical TKA (CMTKA), longer operation times, and intraoperative blood loss (IBL) > 20%. Postoperatively, the HHBL group had significantly more transfusions and longer hospital stays. Logistic regression identified CAD, platelet count, left knee surgery, CMTKA, operation time, and preoperative EPO use as significant factors influencing HHBL. These findings highlight the need for targeted strategies to manage blood loss in knee arthroplasty patients.

This study identifies several factors associated with high hidden blood loss in patients undergoing TKA for osteoarthritis. CAD, CMTKA, prolonged operation time, left-sided surgery, lower preoperative platelet count, and lack of preoperative erythropoietin (EPO) use were significantly linked to HHBL. While these associations highlight potential targets for intervention, further prospective studies are needed to confirm causality.

Sinomenine is an active substance extracted from the traditional Chinese medicine Sinomenium acutum. Sinomenine has been shown to mediate a wide range of pharmacological actions and is known to possess good anti-inflammatory, immunosuppressive, antitumor, neuroprotective, antiarrhythmic and other pharmacological effects. Understanding the underlying mechanisms and the association between the targets and the pharmaceutical effects on different diseases is crucial to the discovery and design of new treatment strategies. In this review, we aim to give a systematic and comprehensive overview of the research progress of sinomenine over the past 20 years. We first describe the metabolism of sinomenine in vivo and then summarize the pharmacological actions of sinomenine on different diseases. Furthermore, the potential binding properties of sinomenine and the potential of developing new sinomenine-based drugs are also reviewed. LINKED ARTICLES: This article is part of a themed issue Natural Products and Cancer: From Drug Discovery to Prevention and Therapy. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.10/issuetoc.

Knee osteoarthritis (OA) and atopic diseases are both characterized by chronic inflammation, yet their potential relationship remains unexplored. This study investigates whether atopic diseases are associated with an increased risk of knee OA in a large nationwide cohort. We conducted a nationwide cohort study using data from the Korean National Health Insurance Service (NHIS), including 880,300 individuals aged ≥ 50 years. Atopic disease was defined as ≥ 3 outpatient visits for asthma, allergic rhinitis, or atopic dermatitis. Knee OA incidence was identified using ICD-10 codes, and hazard ratios (HRs) were estimated using Cox proportional hazards models. Individuals with atopic diseases had a 36% higher risk of developing knee OA compared to those without (HR = 1.36, 95% CI: 1.35-1.37). A dose-response relationship was observed, with risk increasing progressively in individuals with multiple atopic conditions (HR = 1.44 for two conditions; HR = 1.51 for all three conditions). Subgroup analyses indicated that this association was strongest in younger individuals (50-59 years) and males. The results indicate a significant association between atopic diseases and an increased risk of knee OA, which was strongest in younger individuals. Further research is needed to understand the potential role of atopic-specific inflammation on OA development, and any potential implications for targeted therapies.

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetylase, in mediating deacetylation during ferroptosis in OA chondrocytes remains underexplored. This study aimed to elucidate the mechanisms by which Sirt1 influences chondrocyte ferroptosis in the development of OA.

In vitro and in vivo models of OA were established using IL-1β-induced mouse chondrocytes and a destabilization of the medial meniscus (DMM) mouse model, respectively. Ferroptosis was evaluated through measurements of cell viability, lactate dehydrogenase (LDH) release, intracellular levels of Fe2+, glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (ROS), propidium iodide staining, and Western blot analysis. The underlying mechanisms were further investigated using quantitative real-time polymerase chain reaction, Western blotting, immunoprecipitation (IP), co-immunoprecipitation (Co-IP), and glutathione-S-transferase pulldown assays. In vivo validation was performed via Safranin O staining.

IL-1β induced ferroptosis and increased histone acetylation, effects that were partially reversed by Sirt1 overexpression. Mechanistically, Sirt1 overexpression upregulated ferritin light polypeptide (Ftl) expression by deacetylating Ftl at the K181 residue. Ftl knockdown inhibited the ferroptosis-enhancing effect of Sirt1 overexpression in chondrocytes. In vivo studies showed that Sirt1 overexpression mitigated the progression of OA and reduced ferroptosis in the DMM-induced OA mouse model.

Our findings confirm that Sirt1 overexpression promotes Ftl expression through deacetylation at the K181 site, thereby suppressing chondrocyte ferroptosis and attenuating the progression of OA. These results suggest a potential therapeutic target for OA treatment.

Osteoarthritis (OA) represents a globally prevalent degenerative bone diseases and is the primary contributors to pain and disability among middle-aged and elderly people, thereby imposing significant social and economic burdens. When articular cartilage is in the aging environment, epigenetic modifications, DNA damage and mitochondrial dysfunction lead to cell senescence. Chondrocyte senescence has been identified as a pivotal event in this metabolic dysregulation of the extracellular matrix (ECM). It can affect the composition and structure of ECM, and the mechanical and biological signals transmitted by ECM to senescent chondrocytes affect their physiology and pathology. Over the past few decades, the role of ECM in aging-related OA has received increasing attention. In this review, we summarize the changes of cartilage's major ECM (type II collagen and aggrecan) and the interaction between aging and ECM in OA, and explore therapeutic strategies targeting cartilagae ECM, such as noncoding RNAs, small-molecule drugs, and mesenchymal stem cell (MSC)-derived extracellular vesicles for OA. The aim of this study was to elucidate the potential benefits of ECM-based therapies as novel strategies for the management of OA diseases.

BackgroundSchool teachers often have knee osteoarthritis due to the nature of their work.ObjectiveTo compare the effects of post-isometric exercise and piroxicam on pain and functional impairment in school teachers having knee osteoarthritis.MethodA pragmatic, community-based, double-blinded, randomized clinical trial (IRCT20230202057310N4) was conducted was conducted at Muhammad Physical Therapy Clinic and Rehabilitation Center, Multan, Pakistan from September 2023 to July after approval from the Institutional Ethical Committee (). A total of 70 pre-diagnosed osteoarthritis patients were randomly assigned to two groups after enrollment using the lottery method. Patients of Group A were treated with post-isometric exercises for 12 weeks (3 sessions per week and each session lasted for 45 min), while those in Group B were given piroxicam (given orally 20 mg twice a day for 12 weeks). At baseline and the 18th session, pain and daily activities were measured using the Pain Catastrophizing Scale (PCS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, and Numerical Pain Rating Scale (NPRS), biochemical (ESR, CRP, and WBCs) and radiological (X-rays) parameters were evaluated. The data was analyzed by using SPSS-23. The independent t-test compared differences between two unrelated groups while the paired t-test assessed differences within the same group. P-value <0.005 was considered significant.ResultsOut of 70 patients, 68 patients were assessed and there were 46 females and 21 males. The results showed a highly significant improvement in flexion (p = 0.001), WOMAC ADLs (p = 0.001), WOMAC stiffness (p = 0.004), PCS (p = 0.001) in group-A than group-B. Similarly, there was a highly significant improvement in NPRS (p = 0.001), WOMAC pain (p = 0.001), WBCs % (p = 0.002), ESR (p = 0.002) and CRP (p = 0.003) in group-B than group-A, underscoring the effectiveness of the post-isometric exercises.ConclusionThese findings suggest that post-isometric exercises could be a more beneficial treatment option than piroxicam for knee osteoarthritis. The practical implications of this research are significant, as it demonstrates that post-isometric exercises not only enhance functional results but also reduce pain severity, offering a promising alternative to traditional medication.

Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions.

A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed.

Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application.

MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.

This study aimed to evaluate the early clinical and radiological outcomes of robot assisted total knee arthroplasty, and to determine the efficiency and safety of its bone resection and implant positioning of the novel robot system.

144 patients who underwent primary TKA were enrolled in this prospective, multicenter RCT conducted in three hospitals. five patients were lost to follow-up at six weeks after surgery. Therefore, 139 patients (73 in the RA TKA group and 66 in the CI TKA group) remained in the final analysis. The primary outcome was the rate of patients whose postoperative alignment was less than 3° deviated from the planned evaluated by full-length weight-bearing X-rays of the lower limb at 12 weeks postoperatively. Secondary outcomes included coronal and sagittal alignment of the components, operation times, blood loss, 12-week range of motion(ROM), 12-week postoperative functional outcomes and satisfaction evaluated by the American Knee Society Score (KSS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and adverse events (AEs).

At 12 weeks postoperatively, we found the rate of radiographic inliers was significantly higher in the RA TKA group (90.4% vs. 59.1%; p < 0.05). The difference between planned and postoperative frontal femoral component (FFC) angle, frontal tibia component (FTC) angle and lateral femoral component (LFC) angle are significantly smaller in the RA TKA group (p < 0.05). The operation time was significantly longer in the RA TKA group than in the CI TKA group (133.01 vs. 92.33 min; p < 0.05). There was no significant difference in blood loss, 12-week ROM, 12-week postoperative functional outcomes and satisfaction evaluated by KSS and WOMAC scores. There were no AEs or SAEs that were determined to be "related" to the robotic system.

The novel robot assisted TKA is safe and more precise in bone resection and implant positioning as demonstrated in this trial.

Osteoarthritis (OA) is a prevalent and disabling joint condition that affects millions worldwide, particularly in the knee joint, and it presents limited therapeutic options. Platelet-rich plasma (PRP) and hyaluronic acid (HA) have emerged as promising intra-articular treatments. This study aimed to compare the effects of single-dose PRP and HA on pain, functionality, and stiffness in patients with knee OA over a 12-week follow-up period.

A retrospective analysis was conducted on 64 patients who underwent single-dose intra-articular HA or PRP treatment for knee OA between December 2021 and June 2022. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Patient satisfaction was evaluated using a Likert scale. Appropriate statistical analyses were performed to compare treatment outcomes and p<0.05 was considered statistically significant.

Both PRP and HA treatments led to significant improvements in pain, functionality, and stiffness over the 12-week follow-up period. VAS pain scores decreased significantly in both groups, but a greater reduction was observed in the HA group. Additionally, the HA group exhibited superior improvement in the WOMAC physical function score at the 4-week mark (p=0.047).

This study is another novel contribution to the growing literature on treatment of PRP and HA treatments for knee OA, where we highlighted the potential benefits of single-dose HA in alleviating pain and enhancing physical function.

Exercise therapy is a core intervention for knee osteoarthritis (KOA). For KOA patients, active and passive stretching exercises can relieve joint pain and restore joint function. Heel kicking exercise (HKE) is a dynamic stretching method designed by the authors to rapidly reduce knee pain and restore joint function in patients with KOA. This randomized controlled trial was conducted to determine the efficacy of HKE for pain and joint function in patients with KOA.

A total of 68 patients with KOA were included in this study. Eight patients were excluded, resulting in random allocation into a control group (N = 29, 1 lost to follow-up) and an observation group (N = 30). Both groups received traditional Chinese medicine hot compress therapy, oral administration of celecoxib capsules, and quadriceps contraction exercises. The control group additionally performed static stretching exercises targeting the quadriceps, hamstrings, and gastrocnemius muscles; conversely, the observation group performed in HKE. Changes in Western Ontario and McMaster Universities Osteoarthritis Index pain and stiffness indices, knee joint range of motion, Five-Times-Sit-to-Stand Test, Timed Up and Go Test, and Six-Minute Walk Test were assessed before treatment initiation and after 2 weeks.

Before treatment, there were no significant differences in the Western Ontario and McMaster Universities Osteoarthritis Index pain and stiffness score, joint range of motion, Five-Times-Sit-to-Stand Test, Timed Up and Go Test, and Six-Minute Walk Test levels between the 2 groups (P > .05). After treatment, the observation group outperformed the control group across all indicators (P < .05, P < .01). Patients' satisfaction within 2 groups were investigated, which showed that patients' satisfaction within the observation group were better than those in the control group (P < .01).

HKE is an effective and safe exercise therapy that significantly alleviates knee pain in patients with KOA while restoring joint function.

Obesity is considered an important risk factor for osteoarthritis (OA), with conicity index (C-index), relative fat mass (RFM) are two novel anthropometric measures of obesity. To investigate the association between OA and these two indicators, we conducted this study.

We used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the association between C-index, RFM, and OA. First, the participants were divided into two groups according to whether they had OA, and we compared the baseline characteristics of the two groups. Then, C-index and RFM were divided into quartiles (Q1, Q2, Q3, Q4) for multivariate regression analysis. Additionally, we applied restricted cubic spline (RCS) to assess whether the relationship is non-linear. Finally, we conducted a subgroup interaction analysis to investigate whether this relationship varies across different subgroups.

The study included 34,707 participants, with a weighted OA prevalence of 7.7%. Significant differences in C-index and RFM were observed between OA and non-OA groups. Treating C-index and RFM as categorical variables, logistic regression showed significantly higher OA risk in Q4 compared to Q1: for C-index, Q4 (OR = 1.60; 95% CI: 1.33-1.93; P < 0.001); for RFM, Q4 (OR = 2.07; 95% CI: 1.57-2.73; P < 0.001). The RCS results show that the relationship between C-index and OA is non-linear, while the relationship between RFM and OA is linear. Subgroup interaction analysis showed some interaction effects.

This study reveals detailed relationships between C-index, RFM, and OA, which may be better indicators of obesity in assessing OA risk.

Osteoarthritis (OA) is a widely encountered degenerative joint disorder marked by gradual cartilage deterioration, inflammation, and pain, which collectively impose considerable strain on global healthcare systems. While traditional therapies typically offer relief from symptoms, they do not tackle the core pathophysiological aspects of the disease. Regenerative medicine has recently risen as a promising field for addressing OA, capitalizing on the regenerative capabilities of stem cells and growth factors to foster tissue healing and renewal. This thorough review delves into the most recent progress in stem cell and growth factor treatments for OA, covering preclinical studies, clinical trials, and novel technological developments. We discuss the diverse origins of stem cells, such as mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and adipose-derived stem cells (ASCs), underscoring their therapeutic actions and effectiveness in both preclinical and clinical environments. Moreover, we explore contributions of growth factors like transforming growth factor (TGF)-β, platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF) in modifying OA's pathology and enhancing tissue restoration. Additionally, this review discusses the hurdles and constraints tied to current regenerative strategies, including the standardization of cell sources, the refinement of delivery techniques, and considerations for long-term safety. By meticulously assessing the latest research outcomes and technological breakthroughs, this review aims to shed light on the potential of stem cell and growth factor therapies as forthcoming therapeutic options for OA, thereby propelling forward the domain of regenerative medicine and enhancing clinical results for individuals afflicted with this incapacitating ailment.

There is a clear relationship between osteoarthritis (OA) and micronutrients. Excessive accumulation of micronutrients may play a negative role in aggravating the symptoms of OA. This study aims to sort out the causal relationship between micronutrients (zinc, copper, magnesium, vitamins A, C, E, D, B6, and B12, folic acid, iron, carotene, selenium, calcium, and potassium) and OA. This study used Mendelian randomization (MR) to combining the causal relationship between micronutrients and the risk of OA. Micronutrient-related variants were extracted from a large-scale genome-wide association study (GWAS) database of circulating micronutrients in European populations. Outcome data were from the FINNGEN meta-analysis of OA in participants of European ancestry from the FinnGen Biobank in Finland. The primary analysis was performed using the inverse-variance weighted (IVW) method, and a series of sensitivity analyses and multi-dimensionality analyses were conducted to detect possible violations of the MR assumptions. This study used the IVW method to analyze the causal relationship between 15 micronutrients and OA. The results showed that copper (P = 0.535), selenium (P = 0.463), folic acid (P = 0.664), carotene (P = 0.706), potassium (P = 0.839), vitamin D (P = 0.941), vitamin C (P = 0.928), vitamin B12 (P = 0.859), iron (P = 0.496), vitamin E (P = 0.678), magnesium (P = 0.934), vitamin B6 (P = 0.027), calcium (P = 0.743), and vitamin A (P = 0.368) had no significant causal relationship with OA. Among them, vitamin B6 showed P < 0.05 in the pleiotropy test, indicating the presence of pleiotropy. In contrast, zinc exhibited a significant causal relationship with OA (P < 0.001, OR 95% CI = 1.044 [1.021-1.067]), with sensitivity analyses further validating the robustness and reliability of this finding. This study reveals a causal relationship between zinc and OA, identifying zinc as a risk factor for OA. It provides evidence of causality between zinc and OA, offering novel insights for clinical research, diagnosis, and treatment of OA.

Knee osteoarthritis (KOA) is a common degenerative disease that leads to functional decline in the knee joint and a significant reduction in quality of life. Arthroscopic cartilage transplantation combined with platelet-rich plasma (ACT-PRP) has emerged as a novel treatment method and is gradually being applied to patients with early KOA. This study aimed to evaluate the therapeutic efficacy of ACT-PRP compared to conventional conservative treatment.

Patients diagnosed with KOA who were treated in the Department of Orthopedics at the First People's Hospital of Lianyungang from January 2020 to January 2022 were included in the study. Patients were divided into two groups: the ACT-PRP group, receiving arthroscopic cartilage transplantation combined with PRP, and the conservative treatment group, receiving standard conservative treatment. All patients were followed for six months, and knee function and pain relief were assessed using the Lysholm score, IKDC score, KOOS, and VAS.

A total of 113 patients were enrolled, with 43 in the ACT-PRP group and 70 in the conservative treatment group. Baseline characteristics showed no significant differences (P > 0.05). At the final follow-up, the ACT-PRP group showed greater improvements in knee function and pain relief compared to the conservative treatment group, with significantly higher Lysholm score (P < 0.001), IKDC score (P < 0.001), and KOOS (P < 0.001), and lower VAS (P < 0.001). These findings suggest the ACT-PRP approach is more effective for early knee osteoarthritis.

Arthroscopic cartilage transplantation combined with platelet-rich plasma is significantly superior to conventional conservative treatment in improving knee function, alleviating pain, and enhancing patient satisfaction, making it a recommended option for early KOA.

To compare the efficacy of personalized osteotomies with that of standard osteotomies in treating medial unicompartmental knee osteoarthritis.

The clinical data of 96 patients who were diagnosed with unicompartmental knee osteoarthritis in our group between 2019 and 2023 were retrospectively analysed on the basis of preoperative and postoperative radiological measurements. The knee injury and osteoarthritis outcome score (KOOS), forgotten joint score (FJS), and Lysholm knee score scale (Lysholm) were used to assess the clinical outcome, and complications were observed and recorded.

According to the relevant criteria, 84 of 96 patients were included in this study. All patients were followed for a mean of 31 (range 22-55) months. Fifty-one patients underwent personalized osteotomy procedures, and thirty-three underwent standard osteotomy procedures. The postoperative KOOS Pain (P < 0.0001), KOOS Symptoms (P < 0.0001), KOOS ADL (P < 0.0001), KOOS Sport (P = 0.0023), KOOS QoL (P < 0.0001), Lysholm (P < 0.0001) and FJS (P < 0.0001) scores were higher than those in the standard osteotomy group. Nevertheless, postoperative extension (P = 0.2636) and postoperative flexion (P = 0.3554) were not significantly different.

This was a single-centre, retrospective, short follow-up study with several limitations. However, on the basis of the results of the present study, we believe that the function of the knee after medial unicompartmental knee arthroplasty (mUKA) is affected by the direction of tibial osteotomy. We believe that better clinical results may be obtained when the tibial implant is placed near the preoperative tibial deformity.

Level IV; retrospective case series.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that is primarily managed by improving the destroyed cartilage and reversing subchondral bone remodeling. Total glucosides of white paeony (TGP) capsule primarily contains extracts from the white peony root and has been shown to have various pharmacological effects, but its role in KOA still requires comprehensive evaluation. In this study, we aimed to investigate the protective effect of TGP on knee cartilage and subchondral bone, as well as elucidate the underlying molecular mechanisms. The effect of TGP on KOA progression was evaluated in the destabilization of the medial meniscus (DMM)-induced KOA model of mouse and interleukin (IL)-1β-induced KOA model of primary mouse chondrocytes. In vivo and in vitro experiments demonstrated that TGP had a protective effect on the cartilage. Treatment with TGP could induce the synthesis of critical elements in the cartilage extracellular matrix and downregulate the synthesis of degrading enzymes in the extracellular matrix. Regarding the underlying mechanisms, TGP inhibited the phosphorylation and nuclear translocation of p65 by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. In addition, TGP could reduce the secretion of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α). Moreover, it has a sustained effect on coupled subchondral bone remodeling through regulation of the OPG/RANKL/RANK pathway. In conclusion, TGP may protect articular cartilage by downregulating the NF-κB signaling pathway and may support coupled subchondral bone remodeling by regulating OPG/RANKL/RANK signaling pathway in the DMM-induced KOA model of mouse, suggesting a new therapeutic potential for KOA treatment.

Knee osteoarthritis (KOA) is a common joint disease that affects mobility and daily activities. Instrument-assisted soft tissue mobilization (IASTM) is widely used as a conservative treatment due to its potential effects on soft tissues. This study evaluates the effects of IASTM on pain, range of motion (ROM), health status, and gait kinetics in KOA patients.

  Thirty individuals with unilateral KOA were randomized into two groups: IASTM with routine exercises and sham IASTM with exercises, over four sessions in two weeks. Pain, ROM, and WOMAC scores were assessed pre-treatment and 48 hours post-treatment. Gait kinetics, including vertical ground reaction force and knee adduction moment, were measured at three walking speeds (preferred, fixed, and fast) before and after treatment.

Mixed ANOVA revealed significant improvements in pain, ROM, and WOMAC scores in both groups. The IASTM group showed greater improvements in pain, knee flexion, ankle plantarflexion, and WOMAC pain scores, as indicated by a significant group*time interaction. For kinetics, the only significant finding was a longer time to heel strike transient in the IASTM group. At fast speed, most kinetic variables increased significantly in both groups.

Both IASTM and sham interventions with exercise improved pain and ROM. However, the IASTM group experienced greater improvements. Additionally, IASTM led to a longer time to heel strike transient, suggesting improved shock absorption. Overall, IASTM may serve as a beneficial adjunctive intervention for alleviating symptoms in KOA patients and improving gait under challenging conditions, such as fast-speed walking.

Background and Objectives: The aim of the study was to compare the effectiveness of proprioceptive studies according to radiological stages in patients with knee osteoarthritis and to determine at which stage of the disease it should be added to the rehabilitation program. Materials and Methods: This study is a prospective clinical trial. The study was registered with ClinicalTrials.gov (name of the registry: Evaluation of the Effectiveness of Proprioceptive Training According to Radiological Stages in Patients with Knee Osteoarthritis; trial registration number: NCT06150170; date of registration: 21 November 2023). The patients were divided into two groups, which were Grade 1-2 (Group 1) and Grade 3-4 (Group 2) knee osteoarthritis. Both groups underwent a strengthening plus proprioception exercise 3 times a week for 4 weeks. Our primary scale was the Western Ontario and McMaster Universities Arthritis (WOMAC) scale. The secondary outcome measures were pain intensity level, proprioception, range of motion, muscle strength, physical performance, physical activity, quality of life and patient satisfaction. All evaluations were performed twice, before treatment and after 4 weeks of treatment. Conclusions: After treatment, there were significant improvements in pain, range of motion, proprioception, muscle strength, functionality, physical performance and quality of life in both groups (p < 0.05). There was no significant difference between the total WOMAC scores among groups after treatment (p = 0.086). There was more improvement in hip external rotation range of motion in Group 1 (p = 0.022). No significant difference was found in other secondary outcomes (p > 0.05). As a result of this study, we found that proprioceptive training was effective on pain, joint position sense, range of motion, muscle strength, functionality, physical performance and quality of life in patients with knee osteoarthritis in all radiological stages. However, there was no difference between the groups, except for hip external rotation angles.

Knee osteoarthritis (OA) is the most common degenerative condition, afflicting large number of people globally. Fascia is a three-dimensional network of connective tissue that helps in force transmission along the myofascial chains to bone level causing malalignments and movement dysfunctions. Myofascial dysfunctions have been identified in osteoarthritis of knee as a pain-causing component. Recently, clinicians have aimed a variety of therapeutic techniques at fascia. There is a lack of literature to determine the effect of kinetic chain activation technique (K-CAT) as well as deep front line (DFL) release technique in OA knee.

The current study aimed to determine and compare the effectiveness of DFL release and K-CAT in knee OA.

The study was a randomized clinical trial conducted in an outpatient department of a tertiary care hospital. Thirty-two (n = 32) participants between 45 and 60 years of age with knee osteoarthritis (grades 2 and 3) were included and randomized into two groups based on selection criteria. Group A received DFL myofascial release and Group B received K-CAT, along with common conventional therapy (modality + exercises), three sessions per week for 2 weeks. Pain intensity using Numeric Pain Rating Scale, skyline view of knee radiographic parameters including lateral patellar tilt angle (LPTA) and bisect offset (BO), dynamic knee valgus (DKV) by single leg squat using Kinovea software and quality of life using Knee Injury and Osteoarthritis Outcome Score on day 1 and day 14 of intervention were assessed.

Within-group analyses showed significant improvements in both the groups for pain, BO on x-ray, DKV, and Knee Injury and Osteoarthritis Outcome Score (p < 0.05). LPTA showed statistical significance only in the DFL group. However, between-group comparisons showed no statistical difference in all the outcomes (p > 0.05).

Both DFL myofascial release and K-CAT were found to be equally effective in alleviating pain, improving quality of life and knee malalignments.Trial registered under Clinical Trial Registry of India (CTRI/2023/11/059388).

To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs.

Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II to V, the infiltration of the corresponding compound was carried out spaced one week apart. Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis.

We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed. The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III).

The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

Chronic postsurgical pain (CPSP) after total knee arthroplasty (TKA) is the most common postoperative complication in orthopedics. This study aims to explore the risk factors for CPSP after TKA and construct a nomogram model.

This retrospective study included clinical records of 430 patients who received TKA treatment at Wuhan Fourth Hospital between January 2020 to January 2024. Patients were randomly divided into a training cohort (n=301) and a validation cohort (n=129) in a 7:3 ratios. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and logistic regression analysis were used to identify the independent risk factors, and a predictive nomogram model was established based on the identified risk factors. The concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis were used to assess the predictive accuracy and clinical application value of the nomogram model.

Six risk factors for predicting CPSP were identified, including preoperative anxiety, preoperative depression, preoperative pain, duration of tourniquet use, pain upon discharge, and postoperative C-reactive protein levels. The nomogram model demonstrated sufficient predictive accuracy, with the area under the curve (AUC) values of 0.761 (95% CI: 0.689-0.833) and 0.806 (95% CI: 0.700-0.911) in the training cohort and validation cohort, respectively. The C-index of the training cohort and validation cohort were 0.733 and 0.761, respectively. The calibration curve shows good consistency between the predicted risk of the model and the actual risk of CPSP. Decision curve analysis (DCA) demonstrated the clinical applicability of the model.

The nomogram model established in this study for predicting CPSP after TKA has good predictive value and may be used in clinical practice to identify patients at high risk of developing CPSP after TKA.

The purpose of this study was to evaluate clinical and biochemical efficacy of autologous intraarticular (IA) platelet rich plasma (PRP) compared to saline and to measure effectiveness of single and multiple doses given at monthly intervals for Kellgren-Lawrence (K-L) grade II, III knee osteoarthritis (KOA).

A total of 130 patients were randomised into 4 groups; PRP-1 (n=36), PRP-2 (n=34), PRP-3 (n=32) and saline (NS) (n=28), after approval from institute ethics committee (reference number: TMU/IEC/20-21/091) and was conducted in accordance with Helsinki declaration. Groups PRP-1, PRP-2, PRP-3 received single, double and triple injections of PRP whereas NS group received single saline (0.9%) injection. Assessment of outcome scores (visual analogue scale [VAS] and Western Ontario and McMaster Universities Arthritis Index [WOMAC]) was done at baseline and three, six, nine months post intervention. Serum collagen 2-1 (Coll2-1) estimation at baseline and nine months post-therapy was used for biochemical assessment.

Improvement in VAS and WOMAC was statistically significant and clinically meaningful (Minimal clinically important change [MCIC]; >12% of baseline and ≥2cm difference in mean for WOMAC and VAS, respectively) for groups PRP-1, PRP-2 and PRP-3 in comparison to saline (P<0.05), at every follow-up. PRP groups also exhibited a significant decrease in serum Coll2-1 at 9 months (P<0.05). On comparison among the PRP groups, multiple doses (groups PRP-2 and PRP-3) produced significantly better clinical results than single dose (group PRP-1) (P<0.05), whereas the difference in Coll2-1 levels was significant for group PRP-1 vs PRP-3 only (P<0.05).

PRP results in clinically significant amelioration of functional and pain scores as well as significant reduction in serum levels of Coll2-1 in K-L grade II, III KOA over nine months. These benefits can be accentuated by multiple doses given one month apart.

Platelet-rich plasma (PRP) has emerged as a promising therapeutic intervention for knee osteoarthritis (OA), attracting substantial clinical and research attention. However, the clinical relevance of the treatment benefit remains controversial.

To evaluate the effectiveness of PRP compared with placebo in patients with knee OA in terms of minimal clinically important difference (MCID) and to investigate the possible influence of platelet concentration on the clinical outcome.

Meta-analysis. Level of evidence 1.

The search was conducted on 5 databases (PubMed, Cochrane Library, Scopus, Embase, Web of Science) using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were randomized controlled trials comparing PRP and placebo injections to treat knee OA, written in the English language, with no time limitation. The effects were quantified at 1-, 3-, 6-, and 12-month follow-up points. Visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used, with subanalyses based on platelet concentration performed using a 1,000,000 ± 20% platelets/µL cutoff. The MCID values (VAS, 1.37; WOMAC, 6.4) were used to interpret clinical improvement. The articles' quality was assessed using the Revised Tool for Risk of Bias in Randomized Trials and the Grading of Recommendations Assessment, Development and Evaluation guidelines.

Among the 5499 articles retrieved, 18 randomized controlled trials (1995 patients) were included. PRP presented statistically superior improvements in VAS and WOMAC scores compared with placebo at all follow-up points, exceeding the MCID at 3- and 6-month follow-up points for VAS and at all follow-up points for WOMAC. The subanalysis based on platelet concentration showed that high-platelet PRP provided clinically significant pain relief with the improvement exceeding the MCID compared with placebo at 3-, 6-, and 12-month follow-up points. In contrast, low-platelet PRP failed to offer a clinically perceivable benefit in terms of VAS score. WOMAC results showed that both products provided a clinically significant improvement at 3 and 6 months of follow-up. This benefit was maintained up to the 12-month follow-up in the high-platelet group but not in the low-platelet group, where the improvement compared with placebo did not reach statistical significance.

This meta-analysis showed that PRP offered clinically relevant functional improvement at 1-, 3-, 6-, and 12-month follow-up points and pain relief at 3- and 6-month follow-up points compared with placebo for the treatment of knee OA. Platelet concentration was found to influence treatment efficacy, with high-platelet PRP providing superior pain relief and more durable functional improvement compared with low-platelet PRP.

Delivering immunogloblin G (IgG) to the articular cartilage is a challenge and presents an obstacle in developing therapeutic antibodies for articular diseases. In this study, we focused on binding to the aggrecan-a key component of the cartilage matrix as a proteoglycan-and molecular downsizing to enhance the penetration and retention of antibodies in the articular cartilage.

The control IgG (143 kDa), anti-aggrecan IgG (141 kDa), F(ab')2 (93.0 kDa), and Fab (44.9 kDa) were intra-articularly injected into a rabbit joint, and the concentrations of each molecule in synovial fluid, articular cartilage, and plasma were monitored.

Each molecule exhibited a similar elimination profile in synovial fluid. However, compared to the control IgG, anti-aggrecan IgG showed increased exposure in cartilage. Moreover, anti-aggrecan F(ab')2 exhibited even higher concentrations in cartilage, while the anti-aggrecan Fab demonstrated the highest and most long-lasting concentration profile in cartilage. Fluorescence imaging of the ex vivo cartilage penetration further supported the superior transport of the anti-aggrecan Fab and F(ab')2 compared to the control IgG and the anti-aggrecan IgG.

Our study demonstrates that binding to the cartilage matrix, in addition to molecular size, is important, and that their combination has a synergistic effect on the antibody exposure in the articular cartilage.

To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs.

Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II-V, the infiltration of the corresponding compound was carried out spaced one week apart. Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis.

We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed. The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III).

The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

This study aims to evaluate the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), plateletto-lymphocyte ratio (PLR), and C-reactive protein (CRP)-to-albumin ratio levels between individuals with mild to moderate knee osteoarthritis (OA) and those with severe knee OA.

One hundred eighty-two participants (131 females, 51 males; mean age: 67.7±10.2 years; range, 43 to 91 years) affected by knee OA were involved in the cross-sectional retrospective study between January 2018 and January 2021. Kellgren and Lawrence (K-L) classification was performed in accordance with two-view (lateral and anteroposterior) plain radiograph examinations of each knee. The patients were grouped as follows: 98 patients had mild to moderate knee OA (K-L Grades 1-2), and 84 had severe knee OA (K-L Grades 3-4). Demographic data, neutrophil, monocyte, platelet, and lymphocyte levels, erythrocyte sedimentation rate, albumin, and CRP levels were documented. C-reactive protein-to-albumin ratio, NLR, MLR, and PLR levels were calculated.

The MLR was significantly elevated in the severe knee OA group (p=0.047). A significant positive relationship was found with disease stage, MLR (r=0.206; p=0.005), and NLR levels (r=0.158; p=0.033). Receiver operating characteristic curve analyses for blood MLR demonstrated a sensitivity of 57% and specificity of 60%.

The study results suggest that while MLR and NLR may reflect the inflammatory response in knee OA, they are not highly diagnostic inflammatory markers that can be used to evaluate the severity or prognosis of the disease.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2~4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium. Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Aims: To evaluate the efficacy of stromal vascular fraction (SVF) in treating osteoarthritis (OA). Background: OA is a common degenerative disease, the most important manifestation of which is cartilage destruction and inflammation. The SVF is a mixed group of multiple cells extracted from adipose tissue with a certain ability to promote tissue repair. However, the biological safety and efficacy of human derived SVF in treating OA have not been confirmed. Methods: Seventy-six nude rats were used in this experiment. The rat OA model was constructed with anterior cruciate ligament transection (ACLT). After 4 weeks, SVF cells were injected into the joint cavity once. After 12 weeks, the experimental animals were sacrificed and decalcified sections were subjected to hematoxylin and eosin (H&E), safranine O staining, and AP-PAS staining and immunohistochemistry for inflammation markers. Results: After surgery, the knee joint swells, pain intensifies, and the joint space narrows. The results of H&E, safranine O, and AP-PAS staining showed that the cartilage tissue was damaged in the ACLT-OA group and the treatment of SVF can reduce cartilage degradation. The numbers of ADAMTS-5-, MMP-13-, and IL-1β-positive cells significantly decreased and type II collagen-positive cells were more frequently detected in the ACLT-OA group compared with that in the control group, the treatment of SVF can reduce inflammation. Conclusion: SVF cells can be safely used to treat OA and can both effectively reduce the progression of joint inflammation and promote cartilage regeneration.

The relationship between dietary fiber intake and osteoarthritis (OA) remains unclear. This cross-sectional study, using data from the National Health and Nutrition Examination Survey (NHANES), aimed to examine the association between dietary fiber intake and OA.

A cross-sectional analysis was conducted using NHANES data from 1999 to 2018 to assess the association between dietary fiber intake and OA. Univariate and multivariate weighted logistic regression models, along with restricted cubic spline (RCS) curves, were used to evaluate the relationship.

A total of 30,620 participants were included in this study, of whom 1,864 were diagnosed with OA, yielding a prevalence of 5.74%. Multivariate weighted logistic regression revealed a consistent inverse association between dietary fiber intake and OA (OR = 0.99, 95% CI: 0.97-0.99, P = 0.018). When dietary fiber was treated as a categorical variable, the highest quartile of intake (Q4) was associated with a 27% lower risk of OA compared to the lowest quartile (Q1) (OR = 0.73, 95% CI: 0.58-0.92, P = 0.007). The RCS analysis indicated a non-linear association between dietary fiber intake and OA risk (non-linear P = 0.013). The threshold effect interval suggested that dietary fiber intake in the range of 14.4-26.7 g was associated with a reduced risk of OA, while intake above this level did not provide significant additional protection.

The findings demonstrate a negative linear association between dietary fiber intake and OA risk. Increasing dietary fiber consumption may reduce the risk of OA, offering potential strategies for its prevention and management. Further studies are needed to confirm these findings.

Chronic pain represents the prevailing symptom among patients suffering from knee osteoarthritis (KOA). In KOA, peripheral sensitization is driven by disruptions in subchondral bone homeostasis, local inflammatory responses, and variations in neuropeptide and neurotransmitter levels. Calcitonin, a pivotal peptide involved in bone metabolism, additionally exhibits potent analgesic properties. This study aimed to elucidate the mechanisms underlying calcitonin's neuromodulatory effects related to pain in the treatment of KOA. Three experiments were conducted: (1) assessing calcitonin's therapeutic effects via histomorphology, nociceptive behavioral assessments, and Western blot analysis of proteins; (2) verification of the involvement of neurotransmitters and neuropeptides in calcitonin's action using the Signal Transduction PathwayFinder PCR Array, Bio-Plex suspension chip, and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); and (3) exploration of calcitonin's impact on brain function through functional magnetic resonance imaging (fMRI). Experiment 1 validated calcitonin's efficacy in KOA models. Experiment 2 demonstrated the involvement of the retinoic acid signaling pathway in calcitonin treatment, confirming that its analgesic efficacy is associated with the modulation of neuropeptides and neurotransmitters. Experiment 3 revealed that calcitonin treatment could reverse regional homogeneity and amplitude of low-frequency fluctuations in the hippocampus and tegmental nucleus. The study affirmed the critical role of pain-related neuromodulation mechanisms in calcitonin treatment, demonstrating that its analgesic effects are mediated through the modulation of neurotransmitters, neuropeptides, and brain function, as observed via fMRI. These findings provide a theoretical foundation for the clinical application of calcitonin in the treatment of KOA pain.

To analyze the distribution and drug resistance of pathogens in patients with postoperative infection following knee arthroplasty (TKA) for knee osteoarthritis (KOA) and to explore the effectiveness of high-quality nursing interventions postoperatively.

A retrospective analysis was conducted on clinical data from 87 KOA patients who underwent TKA and developed postoperative wound infections (infection group) at the first Affiliated Hospital of Harbin Medical University from July 2022 to September 2024. Another 87 patients without postoperative infection during the same period were selected as the control group. Deep wound exudate samples were collected from the infection group for pathogen culture, isolation, and identification. Drug susceptibility testing was performed using the K-B disk diffusion method. Additionally, venous blood samples were collected from both the infection and control groups one week after surgery, and serum levels of inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT)] were measured using enzyme-linked immunosorbent assay (ELISA). According to the type of nursing interventions received, the infection group was divided into the conventional care group (n=43, receiving standard orthopedic perioperative care) and the high-quality care group (n=44, receiving comprehensive high-quality care based on routine care). The pain levels [Visual Analog Scale (VAS) scores], knee joint function [Hospital for Special Surgery (HSS) knee scores], activities of daily living (modified Barthel index), and patient satisfaction [Newcastle Satisfaction with Nursing Service (NSNS) scale] were compared between the two groups.

Among the 87 KOA patients with postoperative infection after TKA, 83 patients had a single pathogen infection, and 4 patients had mixed infections with two pathogens, resulting in the cultivation and isolation of 91 pathogens. Of these, 63 (69.23%) were Gram-positive bacteria, primarily Staphylococcus aureus (29.67%) and Staphylococcus epidermidis (17.58%). There were 25 (27.47%) Gram-negative bacteria, primarily Escherichia coli (9.89%) and Pseudomonas aeruginosa (6.59%). Three (3.30%) fungal strains were isolated, all identified as Candida albicans. Gram-positive bacteria showed high resistance to penicillin, benzylpenicillin, ampicillin, erythromycin, clindamycin, ciprofloxacin, and gentamicin, but low resistance to gatifloxacin, and no resistance to vancomycin or teicoplanin. Gram-negative bacteria showed high resistance to ciprofloxacin, levofloxacin, gentamicin, and tobramycin, but low resistance to cefepime, imipenem, meropenem, gatifloxacin, and amikacin. The infection group had significantly higher serum levels of IL-6, TNF-α, and PCT compared to the control group (P<0.05). The VAS scores at 24 hours, 3 days, and 7 days postoperatively were significantly lower in the high-quality care group compared to the conventional care group (P<0.05). The HSS scores and modified Barthel index scores at 3 months postoperatively were higher than preoperative values in both groups, with a greater improvement observed in the high-quality care group (P<0.05). The satisfaction rate in the high-quality care group (93.18%) was significantly higher than in the conventional care group (74.42%) (P<0.05).

The primary pathogens causing postoperative wound infections in KOA patients after TKA are Gram-positive bacteria, with Staphylococcus aureus and Staphylococcus epidermidis being predominant. Serum levels of inflammatory markers are significantly higher in infection patients compared to non-infection patients. High-quality nursing interventions can effectively alleviate postoperative pain, promote recovery of knee joint function, enhance activities of daily living, and improve patient satisfaction.

Knee osteoarthritis, a prevalent musculoskeletal disorder, significantly impacts global health and quality of life. Unfortunately, there is no disease modifying osteoarthritis drugs until now. Krill oil is being explored as a potential alternative, however its efficacy in managing knee symptoms remains unclear. Therefore, the meta-analysis of krill oil in knee osteoarthritis would be interesting and useful.

We conducted a systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases from their inception through November 28, 2024, employing predefined search terms, including "krill oil" and "knee osteoarthritis." We included all relevant randomized controlled trials to ensure a comprehensive analysis. Visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) of pain, stiffness and function were served as primary outcomes. Moreover, blood markers and adverse events were also included.

Five randomized controlled trials involving 730 participants were included. Relative to the usual care group, the krill oil group demonstrated no significant improvement in knee osteoarthritis as measured by visual analog scale; however, it exhibited significant benefits in terms of pain (standardized mean difference [SMD] -0.60; 95% confidence interval [CI] -0.99 to -0.21), stiffness (SMD -0.59; 95%CI -1.04 to -0.14), and functional outcomes (SMD -0.68; 95% CI -1.09 to -0.27) based on WOMAC assessments. Analysis of blood markers also revealed no significant effects of krill oil group compared to the usual care group. Moreover, adverse events in the krill oil group and usual care group also showed no statistical difference. The safety profiles were similar between the 2 groups.

Krill oil presents as a promising safe therapeutic option for knee osteoarthritis; however, its efficacy in pain relief requires further investigation.

Objective: to evaluate the efficacy, safety, and cost-effectiveness of intra-articular hyaluronic acid (IAHA) in treating osteoarthritis (OA), considering innovations in formulations, comparative outcomes, and variability in guidelines. This review aims to synthesize evidence supporting the role of IAHA in multimodal treatment strategies. Materials and Methods: A general, narrative, umbrella review of systematic reviews and meta-analyses was conducted. Clinical practice recommendations and guidelines for IAHA use were also reviewed and evaluated. A comprehensive search was conducted across the main medical data sources. Inclusion criteria focused on studies evaluating the efficacy, safety, and impact of IAHA. Key outcomes included pain reduction (e.g., WOMAC, VAS), functional improvement, safety, and cost-effectiveness. Results: IAHA showed moderate efficacy in pain relief and functional improvement, especially in early-to-moderate OA. The results indicate that hybrid formulations and combination therapies show better clinical outcomes, with expanded efficacy and potential chondroprotection. However, heterogeneity between studies was noted, reflecting variability in patient populations and intervention protocols. International guidelines varied significantly, with some opposing routine use (e.g., AAOS, NICE) and others endorsing IAHA more or less conditionally (e.g., ESCEO, OARSI). Conclusions: IAHA remains a treatment modality in the arsenal of selected populations of people with OA, especially for early and moderate disease. High-quality, standardized studies are still needed to refine IAHA's role and establish personalized guidelines for individual patients. A concerted effort to harmonize global recommendations and economic strategies, such as tiered pricing, can increase equitable access and optimize IAHA's integration of multimodal treatment for OA.

There is a substantial need for ex vivo cartilage damage models to assess new emerging cartilage repair strategies. Ex vivo cartilage explant models have the advantages of achieving standardized and reproducible experimental conditions while maintaining the cells in their native tissue environment. This study aimed to establish a bovine cartilage damage model to evaluate the safety and efficacy of novel cartilage repair therapies. We hypothesized that combining transient exposure to matrix-degrading enzymes with mechanical loading on bovine cartilage would simulate cartilage damage.

Prior to mechanical load, bovine osteochondral plugs underwent a brief 5-minutes treatment with collagenase to induce mild cartilage damage by disrupting the collagen network. To induce a moderate cartilage damage, aggrecanase 1 and aggrecanase 2 were additionally applied to the cartilage for 40 min post-collagenase treatment to degrade aggrecan. Data was analyzed using ANOVA or the Friedman test.

Observations revealed a statistically significant loss of sulphated glycosaminoglycan (sGAG) using both Collagenase Treatment (CT) and Collagenase and Aggrecanase Treatment (CAT), while chondrocytes viability was maintained. Both treatments resulted in a significantly elevated release of inflammation markers during the initial two days, including IL6 and nitric oxide. Collagenase treatment also significantly increased neo-epitopes of aggrecan compared to the untreated plugs at day 7, suggesting endogenous aggrecanase activation upon collagen network disruption. The additional effect of mechanical loading on cartilage degeneration was also explored in the CT group. Mildly damaged cartilage treated solely with collagenase could withstand 1 h per day of cyclical load, at 10-20% compression of cartilage thickness combined with interfacial shear at 25 degrees. However, higher compression levels (20-40% of cartilage thickness) with the same shear stress regimen led to a significant increase in surface chondrocyte death, with no evidence of TUNEL staining.

This study establishes a promising model for evaluating cartilage repair strategies, and screening anti-catabolic drugs, particularly overload-related cartilage damage.

Osteoarthritis (OA) is a prevalent joint disease featured by articular cartilage destruction, causing a huge socio-economic burden worldwide. Repressing endoplasmic reticulum stress (ERS)-mediated ferroptosis can alleviate the progression of OA. Sirtuin 6 (SIRT6) has been shown to suppress OA, but whether SIRT6 can regulate ferroptosis in OA through ERS remains unclear.

In this study, both in vivo and in vitro models of OA were constructed. Micro-CT scans and three-dimensional reconstruction were used to observe the structural injury of knee joint in mice. H&E, TB, SOFG and TUNEL staining were employed to conduct pathological examination of cartilage tissues. The levels of inflammatory factors were analyzed using ELISA. Besides, ERS was assessed by detecting the levels of ERS-related proteins using immunohistochemistry, immunoblotting and immunofluorescence staining. Iron deposition in cartilage tissues was tested by prussian blue staining. Moreover, the contents of intracellular ROS, lipid ROS and Fe2+ were evaluated in IL-1β-stimulated C28/I2 cells. Finally, ML385 (an inhibitor of Nrf2) or tunicamycin (an agonist of ERS) was added to C28/I2 cells to elucidate the exact mechanism.

SIRT6 upregulation reduced the structural injury and inflammation in cartilage tissues of OA mice. ERS and ferroptosis were inhibited by SIRT6 overexpression in cartilage tissues of OA mice and C28/I2 cells exposed to IL-1β. Additionally, SIRT6 upregulation activated Nrf2/HO-1 signaling, as evidenced by elevated nuclear Nrf2 and HO-1 expression. Further, ML385 treatment attenuated the impacts of SIRT6 overexpression on inflammation, ERS and ferroptosis in C28/I2 cells under IL-1β conditions. Particularly, tunicamycin intervention blocked the effects of SIRT6 upregulation on ferroptosis in IL-1β-treated C28/I2 cells.

Collectively, SIRT6 inhibits ERS-medicated ferroptosis through activation of Nrf2/HO-1 pathway in chondrocytes to alleviate OA.

Osteoarthritis (OA) is a common degenerative joint disease characterized by the progressive degradation of articular cartilage, synovial inflammation, and subchondral bone remodeling. This review explores the interplay between aging, PANoptosis, and inflammation in OA progression. Age-related cellular and immune dysfunctions, including cellular senescence, senescence-associated secretory phenotypes (SASPs), and immunosenescence, significantly contribute to joint degeneration. In OA, dysregulated apoptosis, necroptosis, and pyroptosis, particularly in chondrocytes, exacerbate cartilage damage. Apoptosis, mediated by the JNK pathway, reduces chondrocyte density, while necroptosis and pyroptosis, involving RIPK-1/RIPK-3 and the NLRP3 inflammasome, respectively, amplify inflammation and cartilage destruction. Inflammatory cytokines and damage-associated molecular patterns (DAMPs) further enhance these PANoptotic pathways. Current therapeutic strategies primarily focus on anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, with growing interest in anti-senescence drugs targeting cellular senescence and SASP. Additionally, exploring PANoptosis mechanisms offers potential for innovative OA treatments.

Previous studies have shown that hyaluronic acid can delay the progression of knee osteoarthritis. Existing research has extracted a bright red fluid called cell-free fat extract from human adipose tissue, which may play an important role in delaying the progression of osteoarthritis. By comparing with intra-articular injection of hyaluronic acid, this study aimed to evaluate the effects of intra-articular injection of CEFFE on both clinical efficacy and the reduction of bone marrow edema in patients with early to mid-stage knee osteoarthritis.

A total of 48 patients with KOA (Kellgren-Lawrence grade II-III) symptoms were randomly divided into CEFFE group (24 cases) and HA group (24 cases). The patients in the CEFFE group received five injections of CEFFE (2 ml, 1 time/week), and the patients in the HA group received five injections of HA (2 ml, 1 ml/10 mg, 1 time/week). All the patients underwent clinical assessments using rating scales, including VAS, WOMAC and Lysholm Knee Score. These assessments were conducted at pre-treatment and at 3-week, 6-week, 3-month, and 6-month follow-up timepoints post-treatment. The clinical efficacy was evaluated at the 6-month follow-up after the treatment. The changes in subchondral bone marrow edema before and 6 months after treatment were assessed by grading BME on MRI of the affected knees.

A total of 52 knees from 46 patients were included in the final analysis. Comparison of VAS score, WOMAC score, and Lysholm score between the two groups revealed that the differences between pre-treatment and 3 weeks post-treatment were not statistically significant (P > 0.05). For the VAS score and WOMAC score at 6 weeks, 3 months, and 6 months post-treatment, the CEFFE group was lower than the HA group (P < 0.05). For the Lysholm score, the CEFFE group was higher than the HA group (P < 0.05). Compared with pre-treatment, VAS scores and WOMAC scores were lower and Lysholm scores were higher at all post-treatment time points (P < 0.05). At 6 months post-treatment, the clinical efficacy of the CEFFE group was significantly better than that of the HA group (P < 0.05). At 6 months post-treatment, MRI grading showed that subchondral BME was reduced to different degrees in both groups, with the reduction being more pronounced in the CEFFE group (P < 0.05).

This study demonstrated that intra-articular injection of CEFFE into the knee joint could enhance the durability of tissue-specific cells (especially chondrocytes) and improve cellular metabolic processes, preventing the continued progression of osteoarthritis. Both CEFFE and HA were found to improve clinical symptoms and reduced subchondral bone marrow edema in the treatment of early to mid-stage knee osteoarthritis. However, CEFFE was more effective than HA in achieving these outcomes.

Knee osteoarthritis (KOA) has a complex, multifactorial nature with well-established risk factors which may influence treatment decisions. Here we want to identify distinctive characteristics between patients receiving conservative treatment versus total knee replacement (TKR), analyzing both patient-specific and knee-specific features.

This case-control study compared patients assigned to TKR versus conservative management, examining subjects aged 60-75 years with radiographically confirmed KOA (Kellgren-Lawrence grades 2-3), with all participants evaluated by blinded clinicians using validated assessment tools including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Hospital Anxiety and Depression Scale (HADs), Pain Catastrophizing Scale (PCS) and Daily physical activity (DPA) questionnaires. The study employed multivariate analysis of variance for continuous variables at both patient and knee levels, followed by univariate analysis of variance for significant factors, while logistic and linear regression analyses were used to calculate odds ratios, with Bonferroni corrections applied to adjust p-values for multiple comparisons.

Between 2016 and 2020, the study included 87 patients (51 women and 36 men) with a mean age of 67.7 years in both treatment groups, with a slightly higher body mass index (BMI) of 31.9 kg/m2 in the TKR group vs 30.5 kg/m2 in the conservative management group. TKR patients demonstrated significantly worse scores in WOMAC, HADS, and PCS compared to the conservative management group, though DPA levels remained similar between both groups. At the knee level, women demonstrated significantly higher pain sensitivity and central sensitization compared to men, with no differences between conservative and TKR groups.

Patients undergoing TKR exhibited significantly worse baseline clinical outcomes, particularly in WOMAC scores, despite having similar radiographic severity to those receiving conservative treatment, suggesting that functional and symptomatic measures may be more valuable than radiographic findings in determining surgical intervention.