Osteoarthritis Group Research Articles

Quantification of chondroitin sulfate, hyaluronic acid and N-glycans in synovial fluid – A technical performance study

ObjectiveTo validate a quantitative high performance liquid chromatography (HPLC) assay for chondroitin sulfate (CS) and hyaluronic acid (HA) in synovial fluid, and to analyze glycan-patterns in patient samples. DesignSynovial fluid from osteoarthritis (OA, n ​= ​25) and knee-injury (n ​= ​13) patients, a synovial fluid pool (SF-control) and purified aggrecan, were chondroitinase digested and together with CS- and HA-standards fluorophore labelled prior to quantitative HPLC analysis. N-glycan profiles of synovial fluid and aggrecan were assessed by mass spectrometry. ResultsUnsaturated uronic acid and sulfated-N-acetylgalactosamine (ΔUA-GalNAc4S and ΔUA-GalNAc6S) contributed to 95% of the total CS-signal in the SF-control sample. For HA and the CS variants in SF-control the intra- and inter-experiment coefficient of variation was between 3–12% and 11–19%, respectively; tenfold dilution gave recoveries between 74 and 122%, and biofluid stability test (room temperature storage and freeze-thaw cycles) showed recoveries between 81 and 140%. Synovial fluid concentrations of the CS variants ΔUA-GalNAc6S and ΔUA2S-GalNAc6S were three times higher in the recent injury group compared to the OA group, while HA was four times lower. Sixty-one different N-glycans were detected in the synovial fluid samples, but there were no differences in levels of N-glycan classes between patient groups. The CS-profile (levels of ΔUA-GalNAc4S and ΔUA-GalNAc6S) in synovial fluid resembled that of purified aggrecan from corresponding samples; the contribution to the N-glycan profile in synovial fluid from aggrecan was low. ConclusionsThe HPLC-assay is suitable for analyzing CS variants and HA in synovial fluid samples, and the GAG-pattern differs between OA and recently knee injured subjects.

Factors Associated with Osteoarthritis and Their Influence on Health-Related Quality of Life in Older Adults with Osteoarthritis: A Study Based on the 2020 Korea National Health and Nutrition Examination Survey.

Numerous studies have investigated factors associated with osteoarthritis (OA), but few have investigated their effects on psychological problems and health-related quality of life in older adults with OA. We aimed to investigate factors associated with OA and their influence on health-related quality of life in older adults with OA. Among 1394 participants aged ≥65 years, 952 and 442 were categorized into the OA and non-OA groups, respectively. Comprehensive data on demographic characteristics, medical conditions, health-related quality of life, blood test results, and nutritional intake were obtained. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratio for factors associated with OA, including age (odds ratio (OR), 1.038; p = 0.020), female sex (OR, 5.692; p < 0.001), body mass index (OR, 1.108; p < 0.001), hypertension (OR, 1.451; p < 0.050), hyperlipidemia (OR, 1.725; p = 0.001), osteoporosis (OR, 2.451; p < 0.001), and depression (OR, 2.358; p = 0.041). The OA group showed a significantly lower subjective health status (p < 0.001) and higher difficulty in mobility (p < 0.001) and pain/discomfort (p = 0.010) than the non-OA group. The sleeping hours were significantly shorter in the OA group than those in the non-OA group (p = 0.013). OA was a significant contributing factor for unfavorable health-related quality of life in older adults. Controlling the factors associated with OA should be prioritized, and health-related quality of life should be monitored in older adults with OA.

WHICH FACTORS PREDICT A SUCCESSFUL OUTCOME FOLLOWING TOTAL HIP ARTHROPLASTY IN PATIENTS WITH EARLY RADIOLOGICAL OSTEOARTHRITIS?

It is unclear whether patients with early radiographic osteoarthritis (OA) but severe hip symptoms benefit from total hip replacement (THR). We aimed to assess which factors were associated with successful THR in this patient group.From a consecutive series of 1,935 patients undergoing THR we identified 70 (3.6%) patients with early OA (Kellgren and Lawrence (KL) grades 0-2). These were compared with 200 patients with advanced OA (KL grades 3–4). Outcomes were Oxford Hip Scores (OHS), EQ5D and EQ-VAS scores; compared pre-operatively with one year post-operatively. We investigated which clinical and radiographic (plain x-ray, CT, MRI) features predicted successful THR in the early OA group. Success was defined as reaching a postoperative OHS≥42.The early OA group were significantly younger (61 vs 66 years; P=0.0035). There were no significant differences in body mass index, ASA grade or gender. After adjusting for confounders, the advanced OA group had a significantly greater percentage of possible change (PoPC) in OHS (75.8% versus 50.4%; P&lt;0.0001) and improvement in EQ5D (0.151 versus 0.002; P&lt;0.0001). There were no significant differences in complication, revision or readmission rates. In the early OA group, we identified 16/70 (22.9%) patients who had a ‘successful’ THR. Of those with early OA, 38 patients had pre-operative CT or MRI scans. Patients who had a ‘successful’ THR were significantly more likely to have subchondral cysts on CT/MRI (91.7% versus 57.7%; P=0.0362). The presence of cysts on CT/MRI was associated with a significantly greater PoPC in OHS (61.6% versus 38.2%; P=0.0353). The combination of cysts and joint space width (JSW) &lt;1mm was associated with a PoPC of 68%. Plain radiographs were found to significantly underestimate the narrowest JSW compared to CT/MRI (2.4mm versus 1.0mm; P&lt;0.0001).We advise caution in performing THRs in patients with early OA (KL grades 0-2) on plain radiographs. We advocate pre-operative cross-sectional imaging (CT or MRI) in these patients. In the absence of cysts on cross-sectional imaging, a THR seems unlikely to provide a satisfactory outcome.

Long Non-Coding RNA Plasmacytomavariant Translocation1 as ceRNA Adsorbs miR-195 to Relieve Osteoarthritis Symptoms

This study aimed to investigate the role of the long non-coding RNA plasmacytomavariant translocation1 (LncRNA PVT1) in the development of osteoarthritis (OA). The study used mice and performed DMM surgery to establish an OA model. PVT1 and miR-195 agomir were inhibited in the knee joints, and cartilage tissue specimens were collected for gene expression analysis, apoptotic protein detection, histopathological observation, and Mankin’s score evaluation. Enzymelinked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in peripheral blood and cartilage tissues. Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining was used to detect cartilage cell apoptosis. The results indicated that the OA group had higher plasmacytomavariant translocation1 (PVT1) expression and lower miR-195 expression than the sham-operated group. PVT1 was found to act as a molecular sponge for miR-195 through a dual-luciferase reporter assay. Knocking down PVT1 or upregulating miR-195 significantly attenuated inflammation and apoptosis in the bone joints of OA mice. This study provides new insights into the mechanism of OA progression and suggests that regulating the PVT1-miR-195 axis may be beneficial for improving the inflammatory microenvironment of cartilage tissue and apoptosis.

Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2

BackgroundOsteoarthritis (OA) is the most prevalent musculoskeletal disease, imposing a significant public health burden. Exosomes might be an effective means of treating OA. PurposeTo investigate the role of exosomes from adipose tissue-derived stromal cells (ADSCs) in OA. We explored whether exosomes from ADSCs could be absorbed by OA chondrocytes, whether there were differences in miR-429 expression in the exosomes of ADSCs and chondrocytes, and whether ADSC exosomal miR-429 could enhance chondrocyte proliferation to exert therapeutic effects in OA. Study DesignControlled laboratory study. MethodsADSCs were isolated and cultured from 4-week-old Sprague-Dawley rats. ADSCs and chondrocytes were identified by flow cytometry assay and fluorescent staining, respectively. The exosomes were extracted and identified. Exosome transport was verified by cell staining and co-culture. Beclin 1, collagen II, LC3-II/I, miR-429, and FEZ2 mRNA and protein expression were investigated with real-time PCR and western blotting, respectively. Chondrocyte proliferation was investigated with Cell Counting Kit-8 (CCK-8) assay. The association between miR-429 and FEZ2 was verified with luciferase assay. A rat OA model was established and rat knee joint cartilage tissue was examined with hematoxylin–eosin and toluidine blue staining. ResultsBoth ADSCs and chondrocytes secreted exosomes and ADSC-derived exosomes could be absorbed by the chondrocytes. ADCS exosomes contained higher miR-429 levels than chondrocyte exosomes. The luciferase assay demonstrated that miR-429 directly targeted FEZ2. Compared with the OA group, miR-429 promoted chondrocyte proliferation while FEZ2 decreased it. miR-429 promoted autophagy by targeting FEZ2 to ameliorate cartilage injury. In vivo, miR-429 promoted autophagy to alleviate OA by targeting FEZ2. ConclusionADSC exosomes could be beneficial for OA and could be absorbed by chondrocytes to promote chondrocyte proliferation through miR-429. miR-429 ameliorated cartilage injury in OA by targeting FEZ2 and promoting autophagy.

Segmental bioelectrical impedance analysis can detect differences between the affected and non-affected limbs in individuals with hip osteoarthritis

ObjectiveTo analyze the bioelectrical impedance parameters of the lower limbs of individuals with hip osteoarthritis and healthy individuals.DesignCross-sectional study.SettingThe study was carried out at the Hip Surgery Outpatient Clinic.ParticipantsThe volunteers had to be between 45 and 70 years of age, of both sexes, with a clinical and radiological diagnosis of hip osteoarthritis for at least three years, unilateral involvement, or a significant complaint in one hip.MethodsThis was a cross-sectional study. Fifty-four individuals were recruited for the study, 31 individuals with hip osteoarthritis (OA group) and 29 healthy individuals for the control group (C group). Demographic and anthropometric data were collected and then the Numerical Pain Rating Scale, WOMAC, Harris Hip Score, and bioimpedance assessment were applied.Main outcome measure(s)Electrical bioimpedance parameters. Phase angle (PhA), impedance, reactance, and muscle mass.ResultsThere was a significant difference in phase angle (PhA), impedance, and muscle mass at 50 kHz frequency on the side affected by OA when compared to the contralateral side. In the OA group, there was a significant decrease in phase angle (PhA) -0.54 (-0.85 to -0.23) and muscle mass − 0.29 (-0.40 to -0,19), as well as an increase in impedance at the 50 kHz frequency on the side affected by OA when compared to contralateral side 21.71 (13.69 to 29.74). In the C group, there was no difference between the dominant and non-dominant sides (P > 0.05).ConclusionThe segmental electrical bioimpedance equipment can detect differences between limbs affected and unaffected by hip osteoarthritis.

ATAC-seq reveals the roles of chromatin accessibility in the chondrocytes of Kashin-Beck disease compared with primary osteoarthritis.

Objective: This study aimed to investigate the roles of accessible chromatin in understanding the different pathogeneses between Kashin-Beck disease (KBD) and primary osteoarthritis (OA). Methods: Articular cartilages of KBD and OA patients were collected, and after tissue digestion, primary chondrocytes were cultured in vitro. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) was performed to compare the accessible chromatin differences of chondrocytes between KBD and OA groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were executed for the promoter genes. Then, the IntAct online database was used to generate networks of significant genes. Finally, we overlapped the analysis of differentially accessible region (DAR)-associated genes and differentially expressed genes (DEGs) obtained from whole-genomic microarray. Results: We obtained 2,751 total DARs, which contained 1,985 loss and 856 gain DARs and belonged to 11 location distributions. We obtained 218 motifs associated with loss DARs, 71 motifs associated with gain DARs, 30 motif enrichments of loss DARs, and 30 motif enrichments of gain DARs. In total, 1,749 genes are associated with loss DARs, and 826 genes are associated with gain DARs. Among them, 210 promoter genes are associated with loss DARs, and 112 promoter genes are associated with gain DARs. We obtained 15 terms of GO enrichment and 5 terms of KEGG pathway enrichment from loss DAR promoter genes, and 15 terms of GO enrichment and 3 terms of KEGG pathway enrichment from gain DAR promoter genes. We obtained CAPN6 and other 2 overlap genes from loss DARs-vs-down DEGs, AMOTL1 from gain DARs-vs-down DEGs, EBF3 and other 12 overlap genes from loss DARs-vs-up DEGs, and ADARB1 and other 10 overlap genes from 101 gain DARs-vs-up DEGs. These overlap genes were built into 4 gene interaction networks. Conclusion: FGF7, GPD1L, NFIB, RUNX2, and VCAM1 were the overlapped genes from the DAR-associated genes and DEGs. These genes were associated with the abnormal chondrocyte function, which may play crucial roles in different processes between KBD and OA in the way of accessible chromatin.

Asymmetric Flexion Contracture is Associated With Leg Length Inequality in Patients With Knee Osteoarthritis: Data From the Osteoarthritis Initiative

ObjectiveTo evaluate whether knee flexion contracture (FC) was associated with leg length inequality (LLI) and/or morbidity in knee osteoarthritis (OA). DesignWe accessed 2 databases: (1) the Osteoarthritis Initiative (OAI) cohort, including participants with, or at-risk of OA, and (2) the Ottawa Knee Osteoarthritis cross-sectional database (OKOA), including participants with primary advanced knee OA. Both included demographics, radiographic data, knee range of motion, leg length, pain, and function scales. SettingTertiary care academic rheumatology and orthopedic clinics. ParticipantsPatients with or at-risk of primary OA. We included 881 OAI and 72 OKOA participants (N=953). InterventionNot applicable. Main Outcome MeasuresThe primary outcome tested the association between the difference in knee extensions of the OA and contralateral knees (the knee extension difference, or KExD) and LLI. This was evaluated using bivariate regression, followed by a multivariable linear regression model. ResultsOAI participants had less severe knee OA [Kellgren and Lawrence (KL) score 1.9±1.3] vs OKOA (KL score 3.4±0.6). The KExD correlated with LLI for both databases (OAI: R=0.167; P≤.001; OKOA: R=0.339; P=.004). Multivariable regression showed an effect of KExD on LLI in both databases (OAI: β=0.37[0.18,0.57]; P<.001, OKOA: β=0.73[0.20,1.26]; P=.007). When broken down by subgroup, the OAI moderate-severe OA group showed a significant effect of KExD on LLI (β=0.60 [0.34,0.85]; P<.001). ConclusionsOA-related loss of knee extension was associated with LLI for those with moderate-severe OA. Because LLI correlates with worse knee OA symptoms, discovering an FC should cue clinicians to evaluate for LLI, an easily-treatable finding that may help reduce OA-associated morbidity for those approaching the need for arthroplasty.

Circulating leptin level in osteoarthritis and associations between leptin receptor polymorphisms and disease susceptibility: A meta-analysis.

This study aimed to systemically review the evidence on the relationship between the circulating leptin levels and osteoarthritis (OA), and the association between leptin and leptin receptor (LEPR) polymorphisms and OA susceptibility. To find relevant papers (up to February 2023) examining the association between circulating leptin levels, LEPR polymorphisms, and OA, the PUBMED, EMBASE, and Cochrane databases were searched. We performed a meta-analysis to examine the levels of synovial and serum/plasma leptin in OA patients compared with healthy controls, as well as the relationship between OA and LEPR polymorphisms. Data from 15 investigations, totaling 2197 patients with OA and 2546 controls, were included in the meta-analysis. There were statistically significant differences in the levels of circulating leptin between the OA and control groups (standardized mean difference [SMD] 2.178, 95% confidence interval [CI] 1.208-3.139, P = 0.001). Leptin levels were also substantially greater in European, Asian, and Arab groups among OA patients. After adjusting for age, sex, and/or body mass index, the leptin levels of patients with OA were significantly higher. Similarly, regardless of sample size (n < 100 and n ≥ 100) or year of publication, leptin levels were considerably higher in the OA group. In addition, the synovial leptin level was greater in the OA group than in the control group (SMD 0.783; 95% CI 0.247-1.319, P = 0.004). In the LEPR rs1137101 polymorphism, the OA and AA genotypes were significantly associated (odds ratio 0.282, 95% CI 0.126-0.629, P = 0.002), according to the meta-analysis. Ethnic stratification revealed an association between OA and the LEPR rs1137101 AA genotype in Asian and Arab populations. The results of this meta-analysis indicate that patients with OA had considerably greater levels of circulating leptin than did control individuals. In addition, synovial leptin levels were greater in OA patients than in healthy individuals, and the LEPR rs1137101 polymorphism was linked to an increased risk of developing OA. These results imply that leptin participates in the onset and progression of OA.

Altered gut microbiome profile in patients with knee osteoarthritis.

Osteoarthritis (OA) is a kind of chronic, degenerative disorder with unknown causes. In this study, we aimed to improve our understanding of the gut microbiota profile in patients with knee OA. 16S rDNA gene sequencing was performed to detect the gut microbiota in fecal samples collected from the patients with OA (n = 32) and normal control (NC, n = 57). Then the metagenomic sequencing was used to identify the genes or functions linked with gut microbial changes at the species level in the fecal samples from patients with OA and NC groups. The Proteobacteria was identified as dominant bacteria in OA group. We identified 81 genera resulted significantly different in abundance between OA and NC. The abundance of Agathobacter, Ruminococcus, Roseburia, Subdoligranulum, and Lactobacillus showed significant decrease in the OA compared to the NC. The abundance of genera Prevotella_7, Clostridium, Flavonifractor and Klebsiella were increasing in the OA group, and the families Lactobacillaceae, Christensenellaceae, Clostridiaceae_1 and Acidaminococcaceae were increasing in the NC. The metagenomic sequencing showed that the abundance of Bacteroides stercoris, Bacteroides vulgatus and Bacteroides uniformis at the species level were significantly decreasing in the OA, and the abundance of Escherichia coli, Klebsiella pneumoniae, Shigella flexneri and Streptococcus salivarius were significantly increased in OA. The results of our study interpret a comprehensive profile of the gut microbiota in patients with knee OA and offer the evidence that the cartilage-gut-microbiome axis could play a crucial role in underlying the mechanisms and pathogenesis of OA.

Healthcare utilisation and mortality in people with osteoarthritis in the UK: findings from a national primary care database.

The burden of osteoarthritis (OA) in UK primary care has not been investigated thoroughly. To estimate healthcare use and mortality in people with OA (overall and joint specific). A matched cohort study of adults with an incident diagnosis of OA in primary care were selected for the study using UK national Clinical Practice Research Datalink (CPRD) electronic records. Healthcare utilisation was measured as the annual average number of primary care consultations and admissions to hospital after the index date for any cause and all-cause mortality data in 221 807 people with OA and an equal number of controls (with no OA diagnosis) who were matched to the case patients by age (standard deviation 2 years), sex, practice, and year of registration. The associations between OA and healthcare utilisation and all-cause mortality were estimated using multinomial logistic regression and Cox regression, respectively, adjusting for covariates. The mean age of the study population was 61 years and 58% were female. In the OA group, the median number of primary care consultations per year after the index date was 10.91 compared with 9.43 in the non-OA control group (P = 0.001) OA was associated with an increased risk of GP consultation and admission to hospital. The adjusted hazard ratio for all-cause mortality was 1.89 (95% confidence interval [CI] = 1.85 to 1.93) for any OA, 2.09 (95% CI = 2.01 to 2.19) for knee OA, 2.08 (95% CI = 1.95 to 2.21) for hip OA, and 1.80 (95% CI = 1.58 to 2.06) for wrist/hand OA, compared with the respective non-OA control group. People with OA had increased rates of GP consultations, admissions to hospital, and all-cause mortality that varied across joint sites.

Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis.

We aimed to determine whether altered cartilage echo intensity is associated with knee osteoarthritis (OA) severity and whether the alteration occurs before thinning of the femoral cartilage in knee OA. The medial femoral cartilage thickness and echo intensity of 118 women aged ≥ 50years were assessed using an ultrasound imaging device. Based on the Kellgren-Lawrence (KL) grade and knee symptoms, participants were classified into five groups: control (asymptomatic grades 0-1), early OA (symptomatic grade 1), grade 2, grade 3, and grade 4. Analysis of covariance, with adjusted age and height, and the Sidak post hoc test were used to assess the differences in cartilage thickness and echo intensity in knees with varying OA severity. The echo intensity on longitudinal images, equivalent to the tibiofemoral weight-bearing surface, was significantly higher in the grade 2 group than that in the control group (p = 0.049). However, no significant difference was noted in cartilage thickness (n.s.). In the grades 3 and 4 groups, cartilage thickness became thinner as OA progressed (p < 0.001 and p < 0.001, respectively). However, the cartilage echo intensity was not significantly enhanced compared with that of the grade 2 group (n.s.). There were no significant differences in the cartilage thickness and echo intensity between the early OA and control groups on the longitudinal images (n.s.). The echo intensity of the medial femoral cartilage was high in patients with KL grade 2, without decreased thickness. Our findings suggested that higher echo intensity is a feature of early cartilage degeneration in mild knee OA. Further studies are needed to establish this feature as a useful screening parameter of early cartilage degeneration in knee OA. Level III.

Targeting damaged collagen for intra-articular delivery of therapeutics using collagen hybridizing peptides.

The objective of this study was to investigate the potential of collagen hybridizing peptides (CHPs), which bind to denatured collagen, to extend the retention time of near-infrared fluorophores (NIRF) following intra-articular (IA) injection in rat knee joints. CHPs were synthesized with a NIRF conjugated to the N-terminus. Male Sprague-Dawley rats were assigned to one of four experimental groups: healthy, CHP; osteoarthritis (OA), CHP; healthy, scrambled-sequence CHP (sCHP), which has no collagen binding affinity; or OA, sCHP. Animals in the OA groups received an IA injection of monosodium iodoacetate to induce OA. All animals then received the corresponding CHP injection. Animals were imaged repeatedly over 2 weeks using an in vivo fluorescence imaging system. Joint components were isolated and imaged to determine CHP binding distribution. Safranin-O and Fast Green histological staining was performed to confirm the development of OA. CHPs were found to be retained within the joint following IA injection in both healthy and OA animals for the full study period. In contrast, sCHP signal was negligible by 24-48 h. CHP signal was significantly greater (p < 0.05) in OA joints when compared to healthy joints. At the 2-week end point, multiple joint components retained CHPs, including cartilage, meniscus, and synovium. CHPs dramatically extended the retention time of NIRFs following IA injection in healthy and OA knee joints by binding to multiple collagenous tissues in the joint. These results support the pursuit of further research to develop CHP based therapeutics for IA treatment of OA.

Plasma Levels of MMPs and TIMP-1 in Patients with Osteoarthritis After Recovery from COVID-19.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPS) play a key role in the pathogenesis of osteoarthritis (OA). Recent research showed the involvement of some MMPs in COVID-19, but the results are limited and contradictory. In this study, we investigated the levels of MMPs (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10) and TIMP-1 in the plasma of patients with OA after recovery from COVID- 19. The experiment involved patients aged 39 to 80 diagnosed with knee OA. All study participants were divided into three research groups: the control group included healthy individuals, the group OA included patients with enrolled cases of OA, and the third group of OA and COVID-19 included patients with OA who recovered from COVID-19 6-9 months ago. The levels of MMPs and TIMP-1 were measured in plasma by enzyme-linked immunosorbent assay. The study showed a change in the levels of MMPs in patients with OA who had COVID- 19 and those who did not have a history of SARS-CoV-2 infection. Particularly, patients with OA who were infected with coronavirus established an increase in MMP-2, MMP-3, MMP-8, and MMP-9, compared to healthy controls. Compared to normal subjects, a significant decrease in MMP-10 and TIMP-1 was established in both groups of patients with OA and convalescent COVID-19. Thus, the results suggest that COVID-19 can affect the proteolysis-antiproteolysis system even after a long postinfectious state and may cause complications of existing musculoskeletal pathologies.

High intensity interval training attenuates osteoarthritis-associated hyperalgesia in rats

High-intensity interval training (HIIT) is a physical therapy that may benefit patients with osteoarthritis (OA). Cacna2d1 is a calcium channel subunit protein that plays an important role in the activity of nerve cells. However, there is currently no evidence on HIIT relieving OA-associate hyperalgesia by decreased Cacna2d1. Our study established the OA rat models with intra-articular injection of monosodium iodoacetate (MIA). This experiment was divided into two stages. The first stage comprised three groups: the control, OA, and OA-HIIT groups. The second stage comprised two groups, including the AAV-C and AAV-shRNA-Cacna2d1 groups. OA rats were positioned at the L5–L6 segments, and 20 µl of AAV virus was injected intrathecally. The pain threshold, cartilage analysis, Cacna2d1, and pain neurotransmitters were measured and compared. The pain threshold was significantly lower in OA rats than in control rats from the first to the tenth week. Starting from the sixth week, OA-HIIT rats exhibited significantly increased pain thresholds. The expression of Cacna2d1 increased in OA rats. Moreover, the knockdown of Cacna2d1 significantly down-regulated the expression of c-Fos, SP, and Vglut2 in the posterior horn of the spinal cord. In conclusion, HIIT attenuates OA-associated hyperalgesia, which may be related to the down-regulation of Cacna2d1.

A higher intramuscular fat in vastus medialis is associated with functional disabilities and symptoms in early stage of knee osteoarthritis: a case–control study

BackgroundThe characteristics of muscle degeneration in individual quadriceps in early knee osteoarthritis (OA) and the association of muscle quantity and quality on knee dysfunction remain unclear. This study aimed to clarify the characteristics of muscle degeneration in individual quadriceps muscles in early knee OA and elucidate the association of muscle volume and intramuscular adipose tissue (intraMAT) with knee dysfunction, including functional disabilities, symptoms, and joint morphology.MethodsFifty participants were categorized into early knee OA and healthy control groups. 3.0 T magnetic resonance imaging (MRI) using T1-weighted and Dixon methods and 3D SPACE in the thigh muscle and knee joint regions was performed. Quadriceps muscle volume, intraMAT, and whole-organ MRI score (WORMS) were assessed. The Knee Society Score (KSS) was used to evaluate functional disabilities and knee symptoms. Univariate analysis of variance was conducted with covariates to clarify the differences in muscle volume and intraMAT between the two groups. Multiple linear regression analyses were performed using the KSS function and symptom subcategories and WORMS as dependent variables and muscle volume, intraMAT, and the presence of early knee OA as independent variables, such as potential confounders.ResultsThe quadriceps intraMAT, especially in the vastus medialis (VM), was significantly higher in patients with early knee OA than in healthy controls. The VM intraMAT, not muscle volume, was significantly associated with KSS function [B = − 3.47; 95% confidence interval [CI], − 5.24 to − 1.71; p < 0.001] and symptom scores [B = − 0.63; 95% CI, − 1.09 to − 0.17; p = 0.008], but not with WORMS.ConclusionThese findings suggest that higher VM intraMAT is characteristic of quadriceps muscle degeneration in early knee OA and its increase is associated with functional disabilities and symptoms.

Gene Expression in Glenoid Articular Cartilage Varies Across Acute Instability, Chronic Instability, and Osteoarthritis.

Shoulder instability is a common pathology associated with an elevated risk of osteoarthritis (OA). Little is known about gene expression in the cartilage of the glenohumeral joint after dislocation events, particularly as it relates to the risk of posttraumatic OA. This study tested the hypothesis that gene expression in glenoid cartilage varies among acute instability (<3 dislocations), chronic instability (≥3 dislocations), and OA. Articular cartilage was collected from the anteroinferior glenoid of consenting patients undergoing shoulder stabilization surgery (n = 17) or total shoulder arthroplasty (n = 16). Digital quantitative polymerase chain reaction was used to assess the relative expression of 57 genes (36 genes from OA risk allele studies, 21 genes from differential expression studies), comparing (1) OA versus instability (acute and chronic combined), (2) acute versus chronic instability, (3) OA versus acute instability, and (4) OA versus chronic instability. The expression of 11 genes from OA risk allele studies and 9 genes from differential expression studies was significantly different between cartilage from patients with instability and those with OA. Pro-inflammatory genes from differential expression studies and genes from OA risk allele studies were more highly expressed in cartilage in the OA group compared with the instability group, which expressed higher levels of extracellular matrix and pro-anabolic genes. The expression of 14 genes from OA risk allele studies and 4 genes from differential expression studies, including pro-inflammatory genes, anti-anabolic genes, and multiple genes from OA risk allele studies, was higher in the acute instability group compared with the chronic instability group. Cartilage in the OA group displayed higher expression of CCL3, CHST11, GPR22, PRKAR2B, and PTGS2 than cartilage in the group with acute or chronic instability. Whereas cartilage in both the acute and chronic instability groups had higher expression of collagen genes, cartilage in the OA group had expression of a subset of genes from OA risk allele studies or from differential expression studies that was lower than in the acute group and higher than in the chronic group. Glenoid cartilage has an inflammatory and catabolic phenotype in shoulders with OA but an anabolic phenotype in shoulders with instability. Cartilage from shoulders with acute instability displayed greater (cellular) metabolic activity compared with shoulders with chronic instability. This exploratory study identified genes of interest, such as CCL3, CHST11, GPR22, PRKAR2B, and PTGS2, that have elevated expression in osteoarthritic glenoid cartilage. These findings provide new biological insight into the relationship between shoulder instability and OA, which could lead to strategies to predict and potentially modify patients' risk of degenerative arthritis due to shoulder instability.

Imaging measurement and analysis of related indexes of variation of femoral head rotation center

To provide guidance for hip replacement by analyzing the variation of femoral head rotation center in different hip diseases. A total of 5 459 patients were collected from March 2016 to June 2021, who took positive and proportional plain films of both hips for various reasons. The relative position between the rotation center of the femoral head and the apex of the greater trochanter was measured. The positive variation is more than 2 mm above the top of the great trochanter, and the negative variation is more than 2 mm below the top of the great trochanter. A total of 831 patients with variation of femoral head rotation center were collected and were divided into 4 groups according to different diseases, and the variation was counted respectively. There were 15 cases in the normal group involving 10 cases of positive variation and 5 cases of negative variation. There were 145 cases of avascular necrosis of femoral head involving 25 cases of positive variation and 120 cases of negative variation. There were 346 cases of congenital hip dysplasia involving 225 cases of positive variation(including 25 cases of typeⅠ, 70 cases of type Ⅱ, 115 cases of type Ⅲ and 15 cases of type Ⅳ), and 121 cases of negative variation(including 50 cases of crowe typeⅠ, 60 cases of typeⅡ, 10 cases of type Ⅲ and 1 case of type Ⅳ). There were 325 cases of hip osteoarthritis group involving 45 cases of positive variation and 280 cases of negative variation. There was significant difference in variation of femoral head rotation center among the four groups(P<0.05). There was significant difference in variation of femoral head rotation center among different types of congenital hip dysplasia(P<0.05). There were significant differences in cervical trunk angle and eccentricity among different variations of femoral head rotation center(P<0.05). The variation of femoral head rotation center is related to cervical trunk angle and eccentricity. The variation of femoral head rotation center is an important factor in hip diseases. The variation of femoral head rotation center is different in different hip diseases. Avascular necrosis of the femoral head and osteoarthritis of the hip were mostly negative variations. With the aggravation of congenital hip dysplasia, the variation of femoral head rotation center gradually changed from negative variation to positive variation.The variation of femoral head rotation center should be paid attention to in the preoperative planning of hip arthroplasty. It is of great significance to select the appropriate prosthesis and place the prosthesis accurately.

Metabolomics profiling of seminal plasma in obesity-induced asthenozoospermia.

Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine. This study aims to explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia. We performed non-target metabolomic studies on the seminal plasma of healthy men with normal semen parameters (HN group, n=20), obese men with normal semen parameters (ON group, n=20), and men with obesity-induced asthenozoospermia (OA group, n=20) based on gas chromatography-mass spectrometry. Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways. A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group; 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group; and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis, and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group. Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism were closely related to obesity-induced asthenozoospermia.

Total hip arthroplasty in the treatment of severe stages of osteonecrosis of the femoral head and osteoarthritis: results and complications

BACKGROUND: Nowadays total hip arthroplasty (THA) is the method of choice for the treatment of late stages osteonecrosis of the femoral head (OFH) and osteoarthritis (OA) of the hip joint.&#x0D; OBJECTIVE: To evaluate the efficacy and complication pattern of THA in late stages of OFH and OA.&#x0D; MATERIALS AND METHODS: The study included 74 patients who underwent primary THA for OA stages IIIIV (Kellgren and Lawrence classification) and for OFH stages IIIIV (ARCO classification). Group 1 included 34 patients with OFH stages IIIIV, and group 2 40 patients with OA stages IIIIV. The groups were comparable by gender and age. All patients underwent implantation of endoprosthesis components using press-fit fixation with a metalpolyethylene articulation. Treatment results were assessed with regard to the incidence of complications and functional results at 3, 6 months, 1 and 3 years after THA.&#x0D; RESULTS: In our study, the survival rate of components after THA within 3 years after implantation was 100%. No cases of periprosthetic fracture, periprosthetic infection, and aseptic instability of endoprosthesis components were observed in both groups. The surface inflammation of the postoperative wound was detected in 1 (2.9%) patient in the OFH group and in 1 (2.5%) patient in OA group. Dislocation of the endoprosthesis occurred in 1 patient with OFH; there were no such findings in the OA group. The frequency of peri-implant osteolysis was twice lower (2.5%) in patients with OA compared to OFH group (5.8%). There were no statistically significant differences in the functional results dynamics before and after surgery between the groups (Harris score). The average Harris scale score in patients with OFH was 63 and reached 94 after 3 years; in OA group 58 and 94, respectively.&#x0D; CONCLUSION: THA is an alternative method in the treatment of severe hip arthroplasty. Endoprosthetics using a cementless endoprosthesis with a metalpolyethylene articulation demonstrated high efficacy as well as a low number of complications among patients with OFH and OA. We found no significant difference in THA results in terms of survival, postoperative complications, and functional outcome in patients with OFH and OA. Longer postoperative follow-up is advisable, which may allow us to establish some differences in treatment outcomes.