Is erectile dysfunction associated with osteoarthritis and rheumatoid arthritis? Insights from a population-based study.

Background: The correlation between osteoarthritis (OA) and rheumatoid arthritis (RA), both significant components of arthritis, and erectile dysfunction (ED) has yet to be thoroughly investigated. Aim: In this study we aimed to assess the association of OA and RA with ED. Methods: In this observational study we used data from the National Health and Nutrition Examination Survey, which was conducted between 2001 and 2004. Various statistical analyses were employed to investigate the associations of OA and RA with ED, including multivariable logistic regression analysis and subgroup analysis. Outcomes: The primary outcome for this investigation was arthritis as assessed through self-reporting. Results: In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA populations in comparison to the general population. Additional research is imperative to provide a deeper understanding of these correlations and their potential implications for both pathogenesis and treatment strategies. Clinical Implications: The research outcomes reported here may serve as a valuable guide for clinicians to assist OA and RA patientsin staying vigilant in addressing their sexual health concerns. Strengths and Limitations: We explored the association of OA and RA with ED. However, this is only a cross-sectional study. Conclusion: In this comprehensive nationally representative survey spanning 4 years, our findings revealed a notably elevated incidence of ED within both OA and RA patient populations in comparison to the general population. Ongoing research is imperative to provide a deeper understanding of these correlations.

Diagnostic values and relevant factors of lumbar posterior lesions in axial spondyloarthritis.

OBJECTIVES: To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated. METHODS: This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada-Denmark (CANDEN) magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions. RESULTS: Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The CANDEN scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities. CONCLUSIONS: Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.

Is inflammation a missing link between relative handgrip strength with hyperlipidemia? Evidence from a large population-based study.

BACKGROUND: Relative handgrip strength (RHGS) was positively correlated with healthy levels of cardiovascular markers and negatively correlated with metabolic disease risk. However, its association with hyperlipidemia remains unknown. The present study investigated the link between RHGS and hyperlipidemia, utilizing data from the National Health and Nutrition Examination Survey (NHANES) and further examined the hypothesis that inflammation may serve a mediating role within this relationship. METHODS: Data were extracted from 4610 participants in the NHANES database spanning 2011-2014 to explore the correlation between RHGS and hyperlipidemia using multivariate logistic regression models. Subgroup analyses were conducted to discern the correlation between RHGS and hyperlipidemia across diverse populations. Additionally, smooth curve fitting and threshold effect analysis were conducted to validate the association between RHGS and hyperlipidemia. Furthermore, the potential mediating effect of inflammation on this association was also explored. RESULTS: According to the fully adjusted model, RHGS was negatively correlated with hyperlipidemia [odds ratio (OR) = 0.575, 95% confidence interval (CI) = 0.515 to 0.643], which was consistently significant across all populations, notably among women. Smooth curve fitting and threshold effect analysis substantiated the negative association between RHGS and hyperlipidemia. Moreover, the mediating effects analysis indicated the white blood cell (WBC) count, neutrophil (Neu) count, and lymphocyte (Lym) count played roles as the mediators, with mediation ratios of 7.0%, 4.3%, and 5.0%, respectively. CONCLUSIONS: This study identified a prominent negative correlation between RHGS and hyperlipidemia. Elevated RHGS may serve as a protective factor against hyperlipidemia, potentially through mechanisms underlying the modulation of inflammatory processes.

Association between oxidative balance score and rheumatoid arthritis in female: a cross-sectional study.

OBJECTIVE: Although oxidative stress is a recognized factor of inflammation, the correlation between oxidative balance score (OBS), a biomarker indicating the balance of oxidation and antioxidant, and rheumatoid arthritis (RA), an immune system disease that tends to occur in women, remains unexplored. Hence, the aim of this study was to investigate the potential association between OBS and RA in women. METHODS: Observational surveys were performed by employing information extracted from the National Health and Nutrition Examination Survey (NHANES) for the period 2007-2018. Various statistical techniques were employed to investigate the association between OBS and RA, encompassing multivariable logistic regression analysis, subgroup analyses, smooth curve fitting, and threshold effect analysis. RESULTS: The study included 8219 female participants, including 597 patients with RA. The results showed that higher Total OBS (TOBS) significantly correlated with lower RA prevalence in the entirely modified model [odd ratio (OR) = 0.968; 95% confidence interval (CI) = 0.952 to 0.984; P = 0.0001]. Dietary OBS (DOBS) and lifestyle OBS (LOBS) also negatively correlated with RA. This association was remarkably consistent across TOBS subgroups by age, race, education level, family poverty-to-income ratio (PIR), hypertension and diabetes. Smooth curve fitting and threshold effect analysis also revealed the linear relationship between OBS and RA. CONCLUSIONS: Overall, OBS was negatively associated with RA in female. This study suggested that an antioxidant diet and lifestyle may be promising measures to prevent RA in female.

High-resolution magnetic resonance vessel wall imaging in ischemic stroke and carotid artery atherosclerotic stenosis: A review.

Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis.

Insecticidal activity of the spider neurotoxin PPTX-04 through modulating insect voltage-gated sodium channel.

Ion channels on cell membrane are molecular targets of more than half peptide neurotoxins from spiders. From Pardosa pseudoannulata, a predatory spider on a range of insect pests, we characterized a peptide neurotoxin PPTX-04 with an insecticidal activity. PPTX-04 showed high toxicity to Nilaparvata lugens, a main prey of P. pseudoannulata, and the toxicity was not affected by the resistance to etofenprox (IUPAC chemical name:1-ethoxy-4-[2-methyl-1-[(3-phenoxyphenyl)methoxy]propan-2-yl]benzene, purity: 99%). On N. lugens voltage-gated sodium channel NlNav1 expressed in Xenopus oocytes, PPTX-04 prolonged the channel opening and induced tail currents, which is similar to pyrethroid insecticides. However, PPTX-04 potency on NlNav1 was not affected by mutations conferring pyrethroid resistance in insects, which revealed that PPTX-04 and pyrethroids should act on different receptors in NlNav1. In contrast, two mutations at the extracellular site 4 significantly reduced PPTX-04 potency, which indicated that PPTX-04 would act on a potential receptor containing the site 4 in NlNav1. The result from the molecular docking supported the conclusion that the binding pocket of PPTX-04 in NlNav1 should contain the site 4. In summary, PPTX-04 had high insecticidal activity through acting on a distinct receptor site in insect Nav, and was a potential resource to control insect pests and manage resistance to pyrethroids.

Metagenomic Analyses Reveal Gut Microbial Profiles of Cnaphalocrocis medinalis Driven by the Infection of Baculovirus CnmeGV.

The composition of microbiota in the digestive tract gut is essential for insect physiology, homeostasis, and pathogen infection. Little is known about the interactions between microbiota load and oral infection with baculoviruses. CnmeGV is an obligative baculovirus to Cnaphalocrocis medinalis. We investigated the impact of CnmeGV infection on the structure of intestinal microbes of C. medinalis during the initial infection stage. The results revealed that the gut microbiota profiles were dynamically driven by pathogen infection of CnmeGV. The numbers of all the OTU counts were relatively higher at the early and later stages, while the microbial diversity significantly increased early but dropped sharply following the infection. The compositional abundance of domain bacteria Firmicutes developed substantially higher. The significantly enriched and depleted species can be divided into four groups at the species level. Fifteen of these species were ultimately predicted as the biomarkers of CnmeGV infection. CnmeGV infection induces significant enrichment of alterations in functional genes related to metabolism and the immune system, encompassing processes such as carbohydrate, amino acid, cofactor, and vitamin metabolism. Finally, the study may provide an in-depth analysis of the relationship between host microbiota, baculovirus infection, and pest control of C. medinalis.

Association of reproductive lifespan and age at menopause with depression: Data from NHANES 2005-2018.

BACKGROUND: The association between reproductive lifespan and depression in older women is unclear. We conducted this analysis to explore whether a shorter reproductive lifespan is associated with higher odds of depression, while also considering the age at menarche and age at menopause. METHODS: This observational study used data from the National Health and Nutrition Examination Survey (NHANES), which was conducted between 2005 and 2018. Reproductive lifespan was defined as years from age at menarche to age at menopause. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression models were used to explore the relationship between the association of reproductive life span, age at menarche and age at menopause with the incidence of depression. RESULTS: Totally, 2947 patients aged 60 and above were enrolled in the trial, with 241 individuals (8.18 %) diagnosed with depression. Higher odds of depression were found to be significantly correlated with a shorter reproductive lifespan [Odds Ratio (OR) = 0.95, 95 % Confidence interval (CI) = 0.92-0.98] or an earlier ager at menopause (OR = 0.95, 95 % CI = 0.92-0.99), according to the results of multivariable logistic regression analysis after full adjustment. Subgroup analysis and interaction tests indicated a similar association. LIMITATIONS: The cross-sectional study could not yield any conclusions regarding causality. CONCLUSION: In this large cross-sectional study, our result suggested that populations with a shorter reproductive lifespan or an earlier age at menopause were significantly more likely to have depressive symptoms in older U.S. women. Further large-scale prospective studies are warranted for a comprehensive analysis of the role of the reproductive lifespan and age at menopause in depression.

Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration.

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 â€‹mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti-NF-200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization.

Clinical characteristics and risk factors associated with bone erosion in patients with tophi.

INTRODUCTION: If a large amount of urate crystals is deposited in a joint cavity for an extended period of time, bone erosion will occur and gradually cause skeletal muscle necrosis and joint deformity. The aim of this study was to describe the clinical characteristics and factors associated with bone erosion in gout patients with tophi. METHODS: A total of 210 gout patients with tophi were enrolled and divided into a bone erosion group (n = 135) and a non-bone erosion group (n = 75). Digital radiography (DR) was performed to detect bone erosion in the elbow, wrist, knee, ankle joints, interphalangeal and metatarsophalangeal joints. The clinical characteristics were recorded and compared between the two groups. Multivariate logistic regression analysis was conducted to explore the factors associated with bone erosion. RESULTS: Compared with the non-bone erosion group, the bone erosion group had an older age, longer disease duration of gout and tophi, higher level of serum creatinine (sCr), higher proportion of drinking history and ulceration, and a lower glomerular filtration rate (GFR). Univariate logistic regression analysis results showed that sex, age, body mass index (BMI), gout duration, tophi duration, GFR, white blood cell (WBC) count, sCr level, smoking history, drinking history, and presence of ulceration were associated with bone destruction. Multivariable logistic regression analysis results indicated that tophi duration, drinking history, ulceration and sCr were positively and independently related to bone erosion. CONCLUSIONS: Tophi patients with bone erosion presented different clinical characteristics. Tophi duration, drinking history, ulceration and sCr were associated with bone erosion in gout patients with tophi.

ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3ß/ß-catenin pathway.

BACKGROUND: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS AND RESULTS: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. CONCLUSIONS: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.

Media Search Frequency, Source Credibility About e-Cigarette Health Information, and Motivation to Quit EC Among University Students in Chengdu, China.

Purpose: E-cigarettes (ECs) are gaining popularity among young people. This study aimed to assess university student vapers' search frequency and source credibility of commonly used media in China, and their association with daily EC users' motivation to quit EC use. Participants and Methods: This was a cross-sectional study involving an online quantitative survey in six universities in Chengdu, China. Participants answered questions on their EC use patterns, motivation to quit EC, use frequency and source credibility of media use. Hierarchical linear regression analyses were performed to determine the association between media search frequency and source credibility concerning EC health information with the motivation to quit EC. Results: There were a total of 325 participants (Mean age = 20.43, SD = 1.333). Video platforms and social media were ranked frequently used by the participants and were deemed to be more trustworthy. Perceived trustworthiness of online media was the most influential predictor of motivation to quit EC. Those who reported a higher frequency of accessing video platforms and medical health applications recorded higher motivation to quit EC use. Source credibility of news portals were associated higher motivation to quit EC. The association between higher nicotine dependence and lower motivation to quit EC was attenuated when media source credibility and trustworthiness of online media were added into the fully adjusted regression models. Conclusion: There is an association between media use frequency and source credibility to search for EC health information and motivation to quit vaping. More studies could be conducted to examine the effects of media use content on perceptions towards vaping and their motivation to quit vaping.

The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study.

OBJECTIVES: While lipid metabolism disorder is widely acknowledged as a contributing factor to inflammation, the association between remnant cholesterol (RC), which indicates lipid metabolism, and rheumatoid arthritis (RA) has not been investigated. Accordingly, this study evaluated whether RC is associated with RA disease events. METHODS: Data were collected and specifically extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2008 database. The RC value was derived by subtracting the combined amount of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from the total cholesterol (TC). The association between RC and RA was evaluated using multivariate regression analysis and subgroup analysis. RESULTS: The study analyzed 7777 patients, of which 581 patients (7.47%) were diagnosed with RA. After accounting for different covariates, the multivariate logistic regression analysis revealed a notable correlation between increased RC levels and an increased likelihood of RA (odds ratio OR = 1.54; 95% confidence interval CI: 1.11-2.13; P = 0.0092). The interaction test did not yield statistically significant effects on this association. The linear correlation between RC and RA was observed within restricted cubic spline regression model limitations. CONCLUSION: The results suggest that higher RC levels are associated with increased odds of RA, indicating that RC can serve as a novel and convenient index for forecasting the likelihood of RA in the United States. Additionally, these findings offer insights into early intervention strategies for susceptible populations at risk of developing RA.

Microenvironment-responsive bilayer hydrogel microspheres with gelatin-shell for osteoarthritis treatment.

Osteoarthritis is a long-term degenerative condition of the joints that is characterized by the breakdown of cartilage and inflammation of the synovial membrane. The presence of an inflammatory microenvironment and the degradation of the extracellular matrix produced by chondrocytes leads to the aggravation of cartilage injury, hindering the treatment of osteoarthritis. A promising approach to address this issue is to apply a combined strategy that is sensitive to the specific conditions in osteoarthritic joints and possesses properties that can reduce inflammation and promote cartilage healing. Here, inspired by the structure of chocolate-covered peanuts, we developed an injectable, environment-responsive bilayer hydrogel microsphere using microfluidics technology. The microsphere applied chondroitin sulfate methacryloyl (ChsMA) as its core and was coated with a methacryloyl gelatin (GelMA) shell that was loaded with celecoxib (CLX) liposomes (ChsMA+CLX@Lipo@GelMA). CLX was released from the liposomes when the GelMA shell rapidly degraded in response to the osteoarthritic microenvironment and suppressed the generation of inflammatory agents, demonstrating a beneficial impact of the outer shell in reducing inflammation. While the inner methacryloyl microsphere core degraded, chondroitin sulfate was released to promote chondrocyte anabolism and facilitate cartilage repair. Thus, the synthesized bilayer hydrogel microspheres hold great potential for treating osteoarthritis.

Persistent trigeminal artery in a patient with moyamoya disease:a case report and literature review.

BACKGROUNDS: Persistent trigeminal artery (PTA) is a rare anastomosis between internal carotid artery (ICA) and basilar artery. In rare conditions, the PTA could be combined with others cerebrovascular anomalies, moyamoya disease (MMD) is one of them. CASE PRESENTATION: Here, we reported one rare case of MMD associated with PTA, the patient admitted to our department for severe dizziness and headache, imaging examination suggested MMD combined with right PTA, which arising from the ipsilateral cavernous portion of ICA. The patient received phased bilaterral revascularization with no any complication. In the subsequent follow-up, the patient's symptoms and intracranial vascular condition gradually improved. Moreover, we conducted a literature review of coexistence of PTA and MMD, the results of a web of science regarding such condition, and a deep discussion providing brief insight into the status of co-occurrence of PTA and MMD, including its manifestation, treatment and outcome. CONCLUSIONS: The coexistence of PTA and MMD was rarely reported, the pathogenesis of such condition remains unknown. We found that the features of the coexistence of PTA and MMD were diverse, revascularization might be a feasible for such patient.

Comparison of binding sites and affinity of flavonol-Cu(II) complexes with the same parent nucleus: Synthesis, DFT prediction, and coordination pattern.

This study explores the coordination dynamics between dietary polyphenols, specifically kaempferol, quercetin, and myricetin, and Cu ions in aqueous environments. A novel synthesis method for flavonol-Cu(II) coordination compounds is introduced, effectively reducing interference from free metal ions. Our results reveal consistent binding patterns of Cu ions with flavonols (2:1 ratio of flavonol to Cu(II)), predominantly at the 4,5 sites. Various analytical techniques are used to validate these coordination ratios and sites. The binding affinity of the flavonols for Cu ions follows a descending sequence: myricetin > quercetin > kaempferol. Notably, coordination with Cu ions enhances the free-radical scavenging activities of these flavonols. These findings hold substantial importance for food chemistry, biology, and medicine, providing crucial insights into the way dietary flavonols form stable structures in environments similar to human body fluids and their interactions with metal ions, opening new possibilities for their application and understanding in diverse scientific domains.

A new modified MR dual precision positioning of thin-slice oblique sagittal fat suppression proton density weighted imaging: its diagnostic accuracy in anterior cruciate ligament injury.

To evaluate the diagnostic accuracy of a new modified MR dual precision positioning of thin-slice oblique sagittal fat suppression proton density-weighted imaging (DPP-TSO-Sag-FS-PDWI) sequence in detecting ACL injuries and its grades compared to standard sequences using arthroscopy as the standard reference. 42 patients enrolled in this retrospective study received the 1.5-T MRI with standard sequences and the new modified DPP-TSO-Sag-FS-PDWI sequence, and their arthroscopy results was recorded. The Mc Nemer-Bowker and weighted Kappa was performed to compare the consistency of MRI diagnosis with arthroscopic results. Finally, the diagnostic accuracy was calculated based on the true positive, true negative, false negative and false positive values. The diagnostic consistency of the DPP-TSO-Sag-FS-PDWI were higher than standard sequences for both reader 1 (K = 0.876 vs. 0.620) and reader 2 (K = 0.833 vs. 0.683) with good diagnostic repeatability (K = 0.794 vs. 0.598). Furthermore, the DPP-TSO-Sag-FS-PDWI can classify and diagnose three grades of ACL injury [the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value were more than 84%], especially for grade II injury as the PPV was superior for reader 1 (92.3% vs. 53.9%) and reader 2 (84.6% vs. 69.2%). The new modified DPP-TSO-Sag-FS-PDWI sequence can display the ACL injury on one or continuous levels by maximizing the acquisition of complete ligament shape and true anatomical images, and excluding the influence of anatomical differences between individuals. It can improve the diagnostic accuracy with good repeatability and classify three grades of the ACL injury.

ADAM8 silencing suppresses the migration and invasion of fibroblast-like synoviocytes via FSCN1/MAPK cascade in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease that affects elderly populations worldwide, causing pain and disability. Alteration of the fibroblast-like synoviocytes (FLSs) phenotype leads to an imbalance in the synovial inflammatory microenvironment, which accelerates the progression of OA. Despite this knowledge, the specific molecular mechanisms of the synovium that affect OA are still unclear. METHODS: Both in vitro and in vivo experiments were undertaken to explore the role of ADAM8 playing in the synovial inflammatory of OA. A small interfering RNA (siRNA) was targeting ADAM8 to intervene. High-throughput sequencing was also used. RESULTS: Our sequencing analysis revealed significant upregulation of the MAPK signaling cascade and ADAM8 gene expression in IL-1ß-induced FLSs. The in vitro results demonstrated that ADAM8 blockade inhibited the invasion and migration of IL-1ß-induced FLSs, while also suppressing the expression of related matrix metallomatrix proteinases (MMPs). Furthermore, our study revealed that inhibiting ADAM8 weakened the inflammatory protein secretion and MAPK signaling networks in FLSs. Mechanically, it revealed that inhibiting ADAM8 had a significant effect on the expression of migration-related signaling proteins, specifically FSCN1. When siADAM8 was combined with BDP-13176, a FSCN1 inhibitor, the migration and invasion of FLSs was further inhibited. These results suggest that FSCN1 is a crucial downstream factor of ADAM8 in regulating the biological phenotypes of FLSs. The in vivo experiments demonstrated that ADAM8 inhibition effectively reduced synoviocytes inflammation and alleviated the progression of OA in rats. CONCLUSIONS: ADAM8 could be a promising therapeutic target for treating OA by targeting synovial inflammation.

What do osteoporosis and osteoarthritis have in common? An integrated study of overlapping differentially expressed genes in bone mesenchymal stem cells of osteoporosis and osteoarthritis.

OBJECTIVE: For identification of aberrantly expressed genes in mesenchymal stem cells of osteoporosis (OP) and osteoarthritis (OA), Gene Expression Omnibus (GEO) datasets were integrated to investigate the intersection point. METHODS: GSE35958 (osteoporosis) and GSE19664 (osteoarthritis) datasets were obtained from GEO database. The abnormally expressed genes were analyzed by GEO2R. Functional enrichment was explored by Metascape database and R software. The String database and Cytoscape software were used to build the protein-protein interaction network and identify hub genes. GSE35957 and GSE116925 were used as verification datasets. Single-cell analysis and pseudotime analysis were undertaken. CTDbase, Network Analyst, HPA database, HERB database and MIRW database were used to research the information, tissue and cell distribution, regulation, interaction and ingredients targeting the hub genes. Additionally, in vitro experiments such as RT-PCR, ALP staining and immunofluorescence were undertaken as verification tests. RESULTS: Ten hub genes were identified in this study. All these genes play an important role in bone or cartilage generation. They have diagnostic values and therapeutic potential for OA and OP. Single-cell analysis visualized the cell distribution and pseudotime distribution of these genes. Some potential therapeutic ingredients of these genes were identified, such as curcumin, wogonin and glycerin. In vitro experiments, RT-PCR results showed that COL9A3 and MMP3 were downregulated and PTH1R was upregulated during osteogenic induction of BMSC. Immunohistochemical results showed the expression trend of MMP3 and COL2A1. CONCLUSION: Ten abnormal hub genes of osteoporosis and osteoarthritis were identified successfully by this study. They were important regulatory genes for healthy bone and cartilage. These genes could be the common connections between osteoporosis and osteoarthritis as well as treatment targets. Further study of the regulatory mechanism and treatment effects of these genes would be valuable. The results of this study could contribute to further research.