Synovial Fluid MicroRNA-210 as a Potential Biomarker for Early Prediction of Osteoarthritis

Early detection and treatment are critical in the management of osteoarthritis (OA). OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for the diagnosis and prognosis in OA. In this study, we aimed to explore the clinical significance of miR-210 in synovial fluid samples from 10 healthy volunteers and 20 early-stage OA and 20 late-stage OA patients. miR-210 expression was assessed by real-time RT-PCR. VEGF protein levels were examined by ELISA. The results show that miR-210 is significantly upregulated in early-stage OA and late-stage OA patients compared with healthy individuals. Higher levels of VEGF are also found in OA compared with the control. Moreover, miR-210 levels are positively correlated with VEGF levels, suggesting that miR-210 might contribute to OA development through promoting VEGF expression and angiogenesis. In conclusion, upregulation of miR-210 in synovial fluid may occur in the early stage of OA and can be a useful biomarker for early diagnosis of OA.

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Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Genes ◽

10.3390/genes12070989 ◽

2021 ◽

Vol 12 (7) ◽

pp. 989

Author(s):

Dhanashri Ingale ◽

Priya Kulkarni ◽

Ali Electricwala ◽

Alpana Moghe ◽

Sara Kamyab ◽

...

Keyword(s):

Synovial Fluid ◽

Early Stage ◽

Challenge Test ◽

Degradation Process ◽

Cartilage Degradation ◽

Gene Expressions ◽

Inflammatory Microenvironment ◽

Protein Levels ◽

Advanced Stages ◽

Inflammatory Milieu

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

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sRAGE Downregulates the VEGF Expression in PCOS Ovarian Granulosa Cells

10.21203/rs.3.rs-26984/v1 ◽

2020 ◽

Author(s):

Jingyan Wang ◽

Yichun Guan ◽

Yi Liu ◽

Liang Wang ◽

Zhan Zhang ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Granulosa Cells ◽

Ovarian Tissue ◽

Rt Pcr ◽

Vegf Expression ◽

Vitro Fertilization ◽

Protein Levels ◽

Ovarian Granulosa Cells

Abstract Objective High expression of VEGF in ovarian tissue, serum and follicular fluid of PCOS women is involved in the physiological and pathogenesis processes of PCOS. Our objective was to investigate the effect of sRAGE on VEGF expression and EGF-like growth factor in PCOS ovarian granulosa cells.Methods We collected ovarian granulosa cells of PCOS patients who underwent in vitro fertilization (IVF). Then treatment ovarian granulosa cells with different concentrations of sRAGE. Levels of VEGF, AREG, BTC and EREG mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC and EREG were measured by ELISA.Results Treatment with sRAGE decrease the production of VEGF, and the effects were dependent on the concentrations of sRAGE (P < 0.05). Simultaneously, the expression of the EGF-like growth factors AREG, BTC and EREG were decreased, and the expression were dependent on the concentrations of sRAGE (P < 0.05).Conclusions sRAGE may downregulate VEGF expression in PCOS ovarian granulosa cells,and EGF-like growth factor pathway may be involved in this process.

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Quantitative Analysis of the Expression of Human N-myristoyltransferase 1 (hNMT-1) in Cancers

The Open Biomarkers Journal ◽

10.2174/1875318300902010006 ◽

2009 ◽

Vol 2 (1) ◽

pp. 6-10 ◽

Cited By ~ 3

Author(s):

Lifeng Chen ◽

Binbing Ling ◽

Jane Alcorn ◽

Jian Yang

Keyword(s):

Early Stage ◽

Covalent Attachment ◽

Rt Pcr ◽

Lung Cancers ◽

Protein Substrates ◽

Ovarian Cancers ◽

Potential Biomarker ◽

Study Results ◽

Disease Stages ◽

Kidney Liver

Human N-myristoyltransferase 1 (hNMT-1) catalyzes the covalent attachment of myristic acid to N-terminal glycine residues (myristoylation) of numerous protein substrates. Overexpression of hNMT-1 in colorectal and gallbladder cancers makes it a potential biomarker and drug design target for such cancers. In this study, we investigated hNMT-1 expression during the progression of eight different human cancers using quantitative RT-PCR. The study results showed that hNMT-1 was up-regulated in breast, colon, lung and ovarian cancers but not kidney, liver, prostate and thyroid cancers. This suggests a role for hNMT-1 as a biomarker for detection of breast, colon, lung and ovarian cancers. This study also suggests the available hNMT-1 inhibitors may be potential therapeutic agents against breast and lung cancers through all disease stages, although their use would likely be limited to early stage colon and ovarian cancers.

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Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA

10.1101/2020.09.04.279422 ◽

2020 ◽

Author(s):

Neserin Ali ◽

Aleksandra Turkiewicz ◽

Velocity Hughes ◽

Elin Folkesson ◽

Jon Tjörnstand ◽

...

Keyword(s):

Synovial Fluid ◽

Late Stage ◽

Multilevel Model ◽

Molecular Mechanisms ◽

Early Stage ◽

Meniscal Tear ◽

Knee Oa ◽

Data Independent Acquisition ◽

First Time ◽

Early Oa

AbstractThe underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group.More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.

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Clusterin Is Associated with Systemic and Synovial Inflammation in Knee Osteoarthritis

Cartilage ◽

10.1177/1947603520958149 ◽

2020 ◽

pp. 194760352095814

Author(s):

Tachatra Ungsudechachai ◽

Sittisak Honsawek ◽

Jiraphun Jittikoon ◽

Wanvisa Udomsinprasert

Keyword(s):

Synovial Fluid ◽

Knee Osteoarthritis ◽

Mrna Expression ◽

Early Stage ◽

Characteristic Curve ◽

Synovial Inflammation ◽

Enzyme Linked Immunosorbent Assay ◽

Knee Oa ◽

Protein Levels ◽

Synovial Tissues

Objectives This study aimed to determine possible associations between transcriptional and translational levels of clusterin (CLU) in the systemic and local joint environments with the severity of knee osteoarthritis (OA) and to investigate CLU mRNA expression in knee OA fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor-α. Design Circulating and synovial fluid CLU levels in 259 knee OA patients were quantified using an enzyme-linked immunosorbent assay. Relative CLU mRNA expression in 50 knee OA synovial tissues and 4 knee OA FLSs was determined using real-time polymerase chain reaction. Results Plasma CLU levels of knee OA patients were significantly higher than paired synovial fluid samples. Compared with early-stage knee OA patients, those with advanced-stage OA had considerably increased plasma and synovial fluid CLU levels. There were significant positive associations of plasma and synovial fluid CLU levels with radiographic severity of knee OA. Plasma CLU levels were directly correlated with its synovial fluid levels and high-sensitivity C-reactive protein levels in the patients. Receiver-operating characteristic curve analysis unveiled the potential utility of plasma CLU as a novel biomarker for knee OA severity (AUC = 0.80), with a sensitivity of 71.4% and a specificity of 73.3%. Marked upregulation of CLU mRNA expression was observed in both the inflamed synovial tissues and FLSs of knee OA. Conclusion Increased CLU mRNA and protein levels in the systemic and local joint environments of knee OA might reflect knee OA severity, especially systemic and synovial inflammation.

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Elevated plasma miR-133b and miR-221-3p as biomarkers for early Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-94734-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qihua Chen ◽

Na Deng ◽

Ke Lu ◽

Qiao Liao ◽

Xiaoyan Long ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Elevated Plasma ◽

Rt Pcr ◽

Circulating Micrornas ◽

Non Invasive ◽

Differentially Expressed Mirnas ◽

Mirnas Expression ◽

Early Parkinson’S Disease

AbstractBlood circulating microRNAs (miRNAs) are proposed to be promising biomarkers for many neurodegenerative disorders, including Parkinson’s disease (PD). However, there is a lack of identified differentially expressed miRNAs in PD from different studies. The aim of this study was to evaluate miRNAs expression in PD. We measured plasma circulating miRNA expression in three independent sets with a total of 151 PD patients, 21 multiple system atrophy (MSA) patients and 138 healthy controls using high-throughput RT-PCR. We identified that elevated miR-133b and miR-221-3p discriminated early-stage PD from controls with 94.4% sensitivity and 91.1% specificity. Elevated miR-133b and miR-221-3p distinguished PD from controls with 84.8% sensitivity and 88.9% specificity. In addition, miR-4454 distinguished PD from MSA with 57.1% sensitivity and 82.6% specificity. Hence, elevated miR-133b and miR-221-3p potentially represent good biomarkers for early PD, and a combination of miR-133b, miR-221-3p and miR-4454 has the potential to serve as a non-invasive biomarker for PD diagnosis.

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Identifying Apoptosis-Related Transcriptomic Aberrations and Revealing Clinical Relevance as Diagnostic and Prognostic Biomarker in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.519180 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jinyu Zhu ◽

Bufu Tang ◽

Xiuling Lv ◽

Miaomiao Meng ◽

Qiaoyou Weng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Rna Sequencing ◽

Cox Regression ◽

Risk Group ◽

Early Stage ◽

Prognostic Signature ◽

Sequencing Data ◽

Diagnosis And Prognosis ◽

Potential Biomarker ◽

Diagnostic Models

In view of the unsatisfactory treatment outcome of liver cancer under current treatment, where the mortality rate is high and the survival rate is poor, in this study we aimed to use RNA sequencing data to explore potential molecular markers that can be more effective in predicting diagnosis and prognosis of hepatocellular carcinoma. RNA sequencing data and corresponding clinical information were obtained from multiple databases. After matching with the apoptotic genes from the Deathbase database, 14 differentially expressed human apoptosis genes were obtained. Using univariate and multivariate Cox regression analyses, two apoptosis genes (BAK1 and CSE1L) were determined to be closely associated with overall survival (OS) in HCC patients. And subsequently experiments also validated that knockdown of BAK1 and CSE1L significantly inhibited cell proliferation and promoted apoptosis in the HCC. Then the two genes were used to construct a prognostic signature and diagnostic models. The high-risk group showed lower OS time compared to low-risk group in the TCGA cohort (P < 0.001, HR = 2.11), GSE14520 cohort (P = 0.003, HR = 1.85), and ICGC cohort (P < 0.001, HR = 4). And the advanced HCC patients showed higher risk score and worse prognosis compared to early-stage HCC patients. Moreover, the prognostic signature was validated to be an independent prognostic factor. The diagnostic models accurately predicted HCC from normal tissues and dysplastic nodules in the training and validation cohort. These results indicated that the two apoptosis-related signature effectively predicted diagnosis and prognosis of HCC and may serve as a potential biomarker and therapeutic target for HCC.

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sRAGE downregulates the VEGF expression through EGF-like growth factor signal pathway in PCOS ovarian granulosa cells

10.21203/rs.2.23217/v1 ◽

2020 ◽

Author(s):

Jingyan Wang ◽

Yichun Guan ◽

Yi Liu ◽

Liang Wang ◽

Mingze Du ◽

...

Keyword(s):

Growth Factor ◽

Granulosa Cells ◽

Ovarian Tissue ◽

Signal Pathway ◽

Rt Pcr ◽

Vegf Expression ◽

Vitro Fertilization ◽

Protein Levels ◽

Ovarian Granulosa Cells

Abstract Objective High expression of VEGF in ovarian tissue, serum and follicular fluid of PCOS women is involved in the physiological and pathogenesis processes of PCOS. Our objective was to investigate the effect of sRAGE on VEGF expression and EGF-like growth factor in PCOS ovarian granulosa cells. Methods We collected ovarian granulosa cells of PCOS patients who underwent in vitro fertilization (IVF). Then treatment ovarian granulosa cells with different concentrations of sRAGE. Levels of VEGF, AREG, BTC and EREG mRNA were examined by quantitative RT-PCR. The protein levels of VEGF, AREG, BTC and EREG were measured by ELISA. Results Treatment with sRAGE decrease the production of VEGF, and the effects were dependent on the concentrations of sRAGE ( P <0.05). Simultaneously, the expression of the EGF-like growth factors AREG, BTC and EREG were decreased, and the expression were dependent on the concentrations of sRAGE ( P <0.05). Conclusions sRAGE may downregulate VEGF expression via EGF-like growth factor pathway in PCOS ovarian granulosa cells.

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Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-021-00814-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jingjing Liu ◽

Jigeun Yoo ◽

Jung Yoon Ho ◽

Yuyeon Jung ◽

Sanha Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Healthy Subjects ◽

Early Stage ◽

Roc Curves ◽

Pcr Analysis ◽

Rt Pcr ◽

Potential Biomarker ◽

Exosomal Mirnas ◽

Exosomal Mirna

Abstract Background Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC). Methods In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity. Results Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage (p = 0.018). Conclusions Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v2 ◽

2019 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Inflammatory Mediators ◽

Late Stage ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, the expression of inflammatory mediators is controversial and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study is to identify the SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: The levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured in 86 patients using enzyme-linked immunosorbent assays. Nociceptive pain was measured using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC ) pain score. Neuropathic pain was measured using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods were highly correlated to each other. The worse the pain, the worse the K-L grade and knee function were. The expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS was positively correlated to age, K-L grade, and the WOMAC score and negatively correlated to ROM and TNF-α expression. The VAS was positively correlated to age, K-L grade, and the WOMAC score but negatively correlated to ROM and the levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score was not correlated to any of the measured inflammatory mediators; it correlated to only ROM. The PainDETECT score correlated to only the WOMAC score. The expression of other inflammatory mediators was not correlated to any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α exhibit higher expression in early stage of KOA than the late stage of KOA and correlated to pain. The measured catabolic enzymes and neuropeptides are not correlated to nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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