Role of Matrix Metalloproteinases in Musculoskeletal Diseases

Kumar, Lokender; Bisen, Monish; Khan, Azhar Abbas; Kumar, Pradeep; Patel, Sanjay

doi:10.3390/biomedicines10102477

Cited by 22 publications

(25 citation statements)

References 99 publications

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“…Metalloendopeptidase includes a disintegrin and metalloprotease (ADAM) and matrix metalloproteinases (MMPs), in which MMPs partici in the process of OA through synthesis, degradation, and remodelpateing of extracellular matrix components [32]. Our discoveries are consistent with these studies.…”

Section: Discussionsupporting

confidence: 86%

Screening of diagnostic markers related to immune infiltration in osteoarthritis patients based on machine learning

Wang

et al. 2023

Preprint

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Purpose We analyze the immune infiltration model of osteoarthritis to determine the relevant diagnostic biomarkers (OA), and to provide some help for the treatment and diagnosis of OA. Methods From the Gene Expression Omnibus (GEO) database, we downloaded GSE168505 and GSE114007 gene expression datasets, including 24 patients and 21 healthy controls. The R software Limma package and SVA package were used to analyze the batch effect. We selected differentially expressed genes (DEGs), and we then analyzed the DEGs’ functional enrichment. We performed differential analysis to pick out the differentially expressed immune-related genes (DEIRGs) in the merged data set. We first selected the candidate genes by the least absolute shrinkage and selection operator (LASSO) method, and then further screened the diagnostic markers by support vector machine-recursive feature elimination algorithm (SVM-RFE). In dataset GSE129147, the diagnostic value was determined by drawing the receiver operating characteristic (ROC) curve. In addition, we used the CIBERSORT program to assess the 22 kinds immune cells of infiltration models. Finally, an in vitro cell model of OA was established by interleukin-1β(IL-1β) to verify the bioinformatics results. Results Through differential analysis, 454 differential genes were identified, mainly involved ossification, extracellular matrix organization, collagen − containing extracellular matrix, metalloendopeptidase activity, PI3K − Akt signaling pathway, regulation of cell population proliferation, and other biological processes. We screened BIRC5 and TNFSF11 as candidate biomarkers by machine learning. In the data set GSE129147, BIRC5 and TNFSF11 were verified as diagnostic markers of OA by the ROC curve. The following correlation analysis found that BIRC5 and TNFSF11 were correlated with Mast cells resting, NK cells resting, Monocytes, Plasma cells, Eosinophil, Macrophages M0, and Macrophages M2. The expression of BIRC5 and TNFSF11 was up-regulated in the OA model in vitro. Conclusion We conclude that BIRC5 and TNFSF11 can be biomarkers for diagnosing OA. This discovery provides a direction for the occurrence of OA and the exploration of new treatment methods from the perspective of immunology.

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Section: Discussionsupporting

confidence: 86%

Screening of diagnostic markers related to immune infiltration in osteoarthritis patients based on machine learning

Wang

et al. 2023

Preprint

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“…[72,73] Meanwhile, the another hallmark of the disease is the change in physical microenvironment matrix, especially in ECM stiffness characterized by osteophyte formation. [21,74,75] This is due to the composition changes of the cartilage matrix, characterized by a loss of proteoglycan, [76] changes in collagen type deposition, a scattered distribution of prototypic collagen fibrils [77] and fibrosis of the collagen network. [78,79] The correlation between ECM stiffness and composition has been well discussed.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability

Zhou,

Yang,

Duan

et al. 2023

Adv Healthcare Materials

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It is recognized that the changes in the physical properties of extracellular matrix result in fine‐tuned cell responses including cell morphology, proliferation and differentiation. In this study, a novel patterned equidistant micropillar substrate based on polydimethylsiloxane (PDMS) was designed to mimic the collagen fiber‐like network of the cartilage matrix. By changing the component of the curing agent to an oligomeric base, we obtained micropillar substrates with the same topology but different stiffnesses and found that chondrocytes seeded onto the soft micropillar substrate maintain their phenotype by gathering type II collagen and aggrecan more effectively than those seeded onto the stiff micropillar substrate. Moreover, chondrocytes sensed and responded to micropillar substrates with different stiffnesses by altering the ECM‐cytoskeleton‐focal adhesion axis. We then found that the soft substrate‐preserved chondrocyte phenotype was dependent on the activation of Wnt/β‐catenin signaling at a high expression level. Finally, we indicated the changes in osteoid‐like region formation and cartilage phenotype loss in the stiffened sclerotic area of osteoarthritis mouse cartilage to validate the cell behavior changes triggered by micropillar substrates with different stiffnesses. This study provided the change in cell behaviors that are more similar to those of real chondrocytes at tissue level during the transition from a normal state to a state of osteoarthritis.This article is protected by copyright. All rights reserved

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“…A large number of epidemiological studies have shown that the consumption of tea/green tea reduces various types of cancer [ 7 ]. For example, in a pooled analysis of eight population-based cohort studies, females who consumed green tea showed a decreased risk of total cancer mortality: pooled hazard ratios (HR) = 0.89 (95% confidence intervals (CI) = 0.83–0.96) for the consumption of 1–2 cups/day and HR = 0.91 (95% CI = 0.85–0.98) for the 3–4 cups/day [ 10 ].…”

Section: Anticancer Effects Of Egcgmentioning

confidence: 99%

“…Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteases capable of degrading extracellular matrix proteins [ 6 , 7 , 8 ]. In humans, at least 23 different MMPs have been found [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity

et al. 2023

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Epidemiological studies have shown that the consumption of green tea has beneficial effects against cancer. Basic studies have provided evidence that epigallocatechin gallate (EGCG) is a major contributor to these effects. Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases with the ability to degrade the extracellular matrix proteins and are involved in various diseases including cancer in which MMPs have a critical role in invasion and metastasis. In this review, we discuss the effects of EGCG on several types of MMPs in the context of its anticancer activity. In the promoter region, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species. EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression. Other mechanisms by which EGCG inhibits MMPs include direct binding to MMPs to prevent their activation and downregulation of NF-κB to suppress the production of inflammatory cytokines such as TNFα and IL-1β. Findings from studies on EGCG presented here may be useful in the development of more effective anti-MMP agents, which would give beneficial effects on cancer and other diseases.

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Role of Matrix Metalloproteinases in Musculoskeletal Diseases

Cited by 22 publications

References 99 publications

Screening of diagnostic markers related to immune infiltration in osteoarthritis patients based on machine learning

Screening of diagnostic markers related to immune infiltration in osteoarthritis patients based on machine learning

Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability

Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity

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