TGF-β1-stimulation of matrix metalloproteinase-13 expression by down-regulation of miR-203a-5p in rat osteoblasts

Published on Jul 1, 2019in International Journal of Biological Macromolecules5.162
· DOI :10.1016/J.IJBIOMAC.2019.04.003
S. Saiganesh2
Estimated H-index: 2
,
R. Saathvika2
Estimated H-index: 2
+ 4 AuthorsNagarajan Selvamurugan59
Estimated H-index: 59
Sources
Abstract
Abstract Transforming growth factor-beta1 (TGF-β1) is a pleiotropic and ubiquitous cytokine involved in bone development and bone remodeling. Matrix metalloproteinase-13 (MMP13) plays a role in the degradation of the extracellular matrix (ECM), and the regulation of this gene is critical in bone remodeling. We previously reported that TGF-β1 stimulates MMP13 expression in rat osteoblasts. Recently, studies have examined the regulation of bone metabolism by microRNAs (miRNAs) to determine their therapeutic potential in osteogenesis. Here, we assessed the effect of TGF-β1 on down-regulation of miRNAs that target MMP13 and stimulation of MMP13 expression in osteoblasts. We used in silico analysis and identified 11 specific miRNAs which directly target rat MMP13. Among these miRNAs, miR-203a-5p expression was significantly decreased by TGF-β1-treatment in rat osteoblasts. Transient transfection of a miR-203a-5p mimic into rat osteoblasts reduced MMP13 expression. A luciferase reporter assay confirmed a direct targeting of miR-miR-203a-5p with the 3′ untranslated regions of the MMP13 gene. Hence, we suggest that TGF-β1 stimulated down-regulation of miR-203a-5p, resulting in the stimulation of MMP13 expression in rat osteoblasts. Thus, identification of the role of miR-203a-5p via TGF-β1 and MMP13 in bone remodeling indicated its potential as a biomarker or therapeutic agent for treating bone and bone-related diseases.
📖 Papers frequently viewed together
11 Citations
4 Citations
16 Citations
References62
Newest
#1B. ArumugamH-Index: 6
#2M. VishalH-Index: 3
Last. Nagarajan Selvamurugan (SRM University)H-Index: 59
view all 8 authors...
Abstract Parathyroid hormone (PTH) acts as a regulator of calcium homeostasis and bone remodeling. Runx2, an essential transcription factor in bone, is required for osteoblast differentiation. Noncoding RNAs such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play crucial roles in regulating gene expression in osteoblasts. In this study, we investigated the effects of PTH on osteoblast differentiation via Runx2, lncRNA, and miRNA expression in human bone marrow stromal cells (hBMSCs) an...
21 CitationsSource
#1S. ShreyaH-Index: 2
#2D. MalavikaH-Index: 2
Last. Nagarajan SelvamuruganH-Index: 59
view all 4 authors...
: Formation of new bone by osteoblasts is mediated via the activation of signaling pathways, such as TGF-β, BMP, and Wnt. A number of transcription factors participate in the signaling cascades that are tightly regulated by other regulatory factors. Histone deacetylases (HDACs) are one such class of regulatory factors that play an essential role in influencing chromatin architecture and regulate the expression of the genes that play a role in osteoblast differentiation by the mechanism of deacet...
6 CitationsSource
Abstract Activating transcription factor 3 (ATF3) is a stress-responsive factor that belongs to the activator protein 1 (AP-1) family of transcription factors. ATF3 expression is stimulated by various factors such as hypoxia, cytokines, and chemotherapeutic and DNA damaging agents. Upon stimulation, ATF3 can form homodimers or heterodimers with other members of the AP-1 family to repress or activate transcription. Under physiological conditions, ATF3 expression is transient and plays a pivotal r...
33 CitationsSource
#1Charles J. Malemud (Cornell University)H-Index: 49
An imbalance in gene expressional events skewing chondrocyte anabolic and catabolic pathways toward the latter causes an aberrant turnover and loss of extracellular matrix proteins in osteoarthritic (OA) articular cartilage. Thus, catabolism results in the elevated loss of extracellular matrix proteins. There is also evidence of an increase in the frequency of chondrocyte apoptosis that compromises the capacity of articular cartilage to undergo repair. Although much of the fundamental OA studies...
57 CitationsSource
: Parathyroid hormone (PTH) acts on osteoblasts and functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We previously reported that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13) in rat osteoblasts and that MMP-13 plays a key role in bone remodeling, endochondral bone formation, and bone repair. Recent evidence indicated that microRNAs (miRNAs) have regulatory functions in bone metabolism. In this study, we hypothesized that the...
11 CitationsSource
#1Balasubramanian Arumugam (SRM University)H-Index: 1
#2M. Vairamani (SRM University)H-Index: 28
Last. Nagarajan Selvamurugan (SRM University)H-Index: 59
view all 4 authors...
Transforming growth factor-beta1 (TGF-β1), a highly abundant growth factor in skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a bone transcription factor, is required for TGF-β1-mediated stimulation of MMP-13 expression in osteoblastic cells. In this study, the molecular mechanism responsible for TGF-β1-stimulation of MMP-13 expression via Runx2 in osteoblastic cells was elucidated. TGF-β1...
19 CitationsSource
#1Mamoun AhramH-Index: 19
#2Ebtihal MustafaH-Index: 6
Last. Malek ZihlifH-Index: 12
view all 7 authors...
MicroRNA molecules (miRNAs) play important roles in regulating cell behavior. The expression of certain miRNAs has been shown to be regulated by the androgen receptor (AR), which seems to have a critical role in the tumorigenic process of breast cancer. The differential expression of 84 miRNAs was first examined in three breast cancer cell lines: the luminal MCF-7 and T47D cells and the molecular apocrine MDA-MB-453 cells. Analysis of basal expression of miRNAs revealed that each cell line had d...
13 CitationsSource
#1Farhad Salari (Kermanshah University of Medical Sciences)H-Index: 5
#2Fatemeh Vahedi (McMaster-Carr)H-Index: 12
Last. Mojtaba Sankian (MUMS: Mashhad University of Medical Sciences)H-Index: 22
view all 6 authors...
Abstract Allergen-specific sublingual immunotherapy (SLIT) is well known as an effective and non-invasive route to induce allergy desensitization. The goal of this study was to investigate whether a TAT-fused recombinant allergen could enhance SLIT efficacy. BALB/c mice sensitized to the main allergen (Che a 3) of Chenopodium album pollen were treated sublingually either with rChe a 3 (100 μg/dose) or rTAT-Che a 3 (100 μg/dose), two times per week for eight weeks. SLIT with rTAT-Che a 3 led to s...
4 CitationsSource
#1M. Vishal (SRM University)H-Index: 3
#2Selvaraj Vimalraj (SRM University)H-Index: 17
Last. Nagarajan Selvamurugan (SRM University)H-Index: 59
view all 8 authors...
Abstract Mesenchymal stem cells (MSCs) are multipotent cells and their differentiation into the osteoblastic lineage is strictly controlled by several regulators, including microRNAs (miRNAs). Runx2 is a bone transcription factor required for osteoblast differentiation. Here, we used in silico analysis to identify a number of miRNAs that putatively target Runx2 and its co-factors to mediate both positive and negative regulation of osteoblast differentiation. Among these miRNAs, miR-590-5p was se...
60 CitationsSource
#1Yusaku Osako (Kadai: Kagoshima University)H-Index: 8
#2Naohiko Seki (Chiba University)H-Index: 81
Last. Shoji Natsugoe (Kadai: Kagoshima University)H-Index: 70
view all 12 authors...
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancer...
42 CitationsSource
Cited By4
Newest
#1Xin Yi (PRC: China Medical University (PRC))H-Index: 1
#2Jie Liu (PRC: China Medical University (PRC))H-Index: 1
Last. Qing Zhou (PRC: China Medical University (PRC))H-Index: 1
view all 4 authors...
Abstract Objective This study aimed to provide further information on the exact mechanisms involved in the anti-inflammatory effect of low-intensity pulsed ultrasound (LIPUS) on rabbit temporomandibular joint osteoarthritis (TMJOA) on interleukin-6 (IL-6) production in subchondral bone, IL-6 production in IL-1β stimulated via inhibition of the TGF-β1/Smad3 pathway in mouse embryo osteoblast precursor (MC3T3-E1) cells. Design Bilateral joints were injected with type II collagenase to establish TM...
Source
#1Manju Mohan (University of Madras)H-Index: 1
#2Sridhar Muthusami (Karpagam University)H-Index: 9
Last. Ilangovan Ramachandran (University of Madras)H-Index: 11
view all 6 authors...
Abstract Cellular senescence is a hallmark of aging that is characterized by irreversible cell cycle arrest in response to various stress stimuli. It is a normal physiological event, which plays essential role in development, prevention of cancer, wound healing process, etc. Nevertheless, accumulation of senescent cells is the trigger and forms the basis of aging of a tissue/organ and, thus, the organismal aging. During aging, cells display a senescence-associated secretory phenotype (SASP) that...
Source
Matrix metalloproteinase-13 (MMP-13) plays a predominant role in endochondral bone formation and bone remodeling. Parathyroid hormone (PTH) stimulates the expression of MMP-13 via Runx2, a bone transcription factor in rat osteoblastic cells (UMR106-01), and histone deacetylase 4 (HDAC4) acts as a corepressor of Runx2. Moreover, microRNAs (miRNAs) play an important role in regulating genes posttranscriptionally. Here, we hypothesized that PTH upregulates the miRNAs targeting HDAC4, which could le...
4 CitationsSource
Abstract We previously reported that transforming growth factor-β1 (TGF-β1) stimulated the sustained and prolonged expression of activating transcription factor 3 (ATF3) in highly metastatic and invasive human breast cancer cells (MDA-MB231), in contrast to normal human mammary epithelial cells. However, the mechanism behind the stability of ATF3 expression is not yet known. Based on an in silico approach with co-immunoprecipitation and mass spectrometric analyses, we identified a number of prot...
11 CitationsSource