Dataset Information

Matrix metalloproteinase-13, NF-?B p65 and interleukin-1? are associated with the severity of knee osteoarthritis.

ABSTRACT: Knee osteoarthritis (KOA) is a prevalent disease, especially in the elderly. The present study examined the expression of matrix metalloproteinase-13 (MMP-13), NF-?Bp65 and interleukin (IL)-l? in the synovial tissues of KOA patients and the role of MMP-13 and the NF-?Bp65 signalling pathway in KOA pathogenesis. A total of 100 KOA patients were enrolled in our hospital from December 2015 to December 2017 and were classified into either a mild KOA group (Outerbridge grade 1 and 2) or a severe KOA group (Outerbridge grade 3 and 4). Non-OA patients were included as controls. Synovial tissues from patients in both groups were collected for detection of the mRNA and protein expression of MMP-13, NF-?Bp65 and IL-l?. Synovial tissue slices were subjected to haematoxylin and eosin staining and immunohistochemistry (SP method). Cartilage tissues were observed under a light microscope after Safranin O-fast green staining. Reverse transcription-quantitative PCR and western blot analyses demonstrated that the expression of MMP-13, NF-?Bp65 and IL-l? in the mild and severe groups were substantially upregulated compared with the control group (all P<0.05). A positive correlation between MMP-13 and NF-?Bp65 expression in the KOA synovial tissues was identified (P<0.05). Immunohistochemistry revealed that the expression of MMP-13 and NF-?Bp65 was related to the severity of KOA (MMP-13: severe, 92.54%; moderate, 76.52%; control: 32.14%; and NF-?Bp65: severe, 85.56%; moderate, 48.12%; control: 28.32%). This evidence indicated that the severity of KOA was related to MMP-13 and NF-?Bp65 expression. The NF-?B signalling pathway may be activated during OA progression, which could upregulate the expression of MMP-13 and IL-1? and accelerate the deterioration of articular cartilage.

SUBMITTER: Zhao QH

PROVIDER: S-EPMC7185070 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Matrix metalloproteinase-13, NF-κB p65 and interleukin-1β are associated with the severity of knee osteoarthritis.

Zhao Qing-Hua QH Lin Lu-Pan LP Guo Yu-Xiang YX Zou Rui R Wang Zhen Z Shi Zhong-Ping ZP Fu-Qing Lin L

Experimental and therapeutic medicine 20200320 6

Knee osteoarthritis (KOA) is a prevalent disease, especially in the elderly. The present study examined the expression of matrix metalloproteinase-13 (MMP-13), NF-κBp65 and interleukin (IL)-lβ in the synovial tissues of KOA patients and the role of MMP-13 and the NF-κBp65 signalling pathway in KOA pathogenesis. A total of 100 KOA patients were enrolled in our hospital from December 2015 to December 2017 and were classified into either a mild KOA group (Outerbridge grade 1 and 2) or a severe KOA ...[more]

PMID: 32346426

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Project description:OBJECTIVE:Aberrant posttranscriptional regulation of matrix metalloproteinases (MMPs) by microRNA has emerged as an important factor in human diseases. The aim of this study was to determine whether the expression of MMP-13 in human osteoarthritis (OA) chondrocytes is regulated by microRNA. METHODS:Chondrocytes were stimulated with interleukin-1beta (IL-1beta) in vitro. Total RNA was prepared using TRIzol reagent. Polymerase chain reaction (PCR)-based arrays were used to determine the expression profile of 352 human microRNA. Gene expression was quantified using TaqMan assays, and microRNA targets were identified using bioinformatics. Transfection with reporter construct and microRNA mimic was used to verify suppression of target messenger RNA (mRNA). Gene expression of argonaute and Dicer was determined by reverse transcription-PCR, and expression of protein was determined by immunoblotting. The role of activated MAP kinases (MAPKs) and NF-kappaB was evaluated using specific inhibitors. RESULTS:In IL-1beta-stimulated OA chondrocytes, 42 microRNA were down-regulated, 2 microRNA were up-regulated, and the expression of 308 microRNA remained unchanged. In silico analysis identified a sequence in the 3'-untranslated region (3'-UTR) of MMP-13 mRNA complementary to the seed sequence of microRNA-27b (miR-27b). Increased expression of MMP-13 correlated with down-regulation of miR-27b. Overexpression of miR-27b suppressed the activity of a reporter construct containing the 3'-UTR of human MMP-13 mRNA and inhibited the IL-1beta-induced expression of MMP-13 protein in chondrocytes. NF-kappaB and MAPK activation down-regulated the expression of miR-27b. CONCLUSION:Our data demonstrated the expression of miR-27b in both normal and OA chondrocytes. Furthermore, IL-1beta-induced activation of signal transduction pathways associated with the expression of MMP-13 down-regulated the expression of miR-27b. Thus, miR-27b may play a role in regulating the expression of MMP-13 in human chondrocytes.

Project description:ObjectiveTo compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis.MethodsParticipants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18).ResultsBMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain.ConclusionsTo our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

Project description:Knee osteoarthritis (KOA) is characterized by pain and decreased gait function. We aimed to find KOA-related gait features based on patient reported outcome measures (PROMs) and develop regression models using machine learning algorithms to estimate KOA severity. The study included 375 volunteers with variable KOA grades. The severity of KOA was determined using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). WOMAC scores were used to classify disease severity into three groups. A total of 1087 features were extracted from the gait data. An ANOVA and student's t-test were performed and only features that were significant were selected for inclusion in the machine learning algorithm. Three WOMAC subscales (physical function, pain and stiffness) were further divided into three classes. An ANOVA was performed to determine which selected features were significantly related to the subscales. Both linear regression models and a random forest regression was used to estimate patient the WOMAC scores. Forty-three features were selected based on ANOVA and student's t-test results. The following number of features were selected from each joint: 12 from hip, 1 feature from pelvic, 17 features from knee, 9 features from ankle, 1 feature from foot, and 3 features from spatiotemporal parameters. A significance level of < 0.0001 and < 0.00003 was set for the ANOVA and t-test, respectively. The physical function, pain, and stiffness subscales were related to 41, 10, and 16 features, respectively. Linear regression models showed a correlation of 0.723 and the machine learning algorithm showed a correlation of 0.741. The severity of KOA was predicted by gait analysis features, which were incorporated to develop an objective estimation model for KOA severity. The identified features may serve as a tool to guide rehabilitation and progress assessments. In addition, the estimation model presented here suggests an approach for clinical application of gait analysis data for KOA evaluation.

Dataset Information

Matrix metalloproteinase-13, NF-?B p65 and interleukin-1? are associated with the severity of knee osteoarthritis.

Publications

Matrix metalloproteinase-13, NF-κB p65 and interleukin-1β are associated with the severity of knee osteoarthritis.

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