MicroRNA‐193b‐3p regulates matrix metalloproteinase 19 expression in interleukin‐1β‐induced human chondrocytes

Chang, Zongkun; Meng, Fangang; Zhang, Zhi‐qi; Mao, Guping; Huang, Zhiyu; Liao, Weiming; He, Anbang

doi:10.1002/jcb.26669

Cited by 31 publications

(21 citation statements)

References 34 publications

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“…Cartilage destruction begins when chondrocytes are stimulated by proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-alpha 36 , and anti-inflammatory therapies have been considered as innovative osteoarthritis approaches 27 , 37 . miR-193b-3p was shown to inhibit MMP-19 and iNOS expression in IL-1β-induced human chondrocytes by direct targeting MMP-19 38 . In this study, we found that miR-193b-3p was down-regulated in time (6 h, 12 h, 24 h)- and dose (0, 1, 5, and 10 ng/mL)-dependent manners in chondrocytes stimulated with IL-1β.…”

Section: Discussionmentioning

confidence: 97%

MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3

Meng¹,

Li²,

Zhang³

et al. 2018

Theranostics

112

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Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism.Methods: miR-193b-3p expression was assessed in a human mesenchymal stem cell (hMSC) model of chondrogenesis, in interleukin-1β (IL-1β)-treated primary human chondrocytes (PHCs), and in non-degraded and degraded cartilage. hMSCs and PHCs were transfected with miR-193b-3p or its antisense inhibitor. A direct interaction between miR-193b-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of HDAC3 mRNA was confirmed by performing luciferase reporter assays. Chondrocytes were transfected with miR-193b-3p before performing a chromatin immunoprecipitation assay with an anti-acetylated histone H3 antibody. To investigate miR-193b-3p-transfected PHCs in vivo, they were seeded in tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffolds, which were then implanted in nude mice. In addition, plasma exosomal miR-193b-3p in samples from normal controls and patients with osteoarthritis (OA) were measured.Results: miR-193b-3p expression was elevated in chondrogenic and hypertrophic hMSCs, while expression was significantly reduced in degraded cartilage compared to non-degraded cartilage. In addition, miR-193b-3p suppressed the activity of reporter constructs containing the 3′-UTR of HDAC3, inhibited HDAC3 expression, and promoted histone H3 acetylation in the COL2A1, AGGRECAN, COMP, and SOX9 promoters. Treatment with the HDAC inhibitor trichostatin A (TSA) increased cartilage-specific gene expression and enhanced hMSCs chondrogenesis. TSA also increased AGGRECAN expression and decreased MMP13 expression in IL-1β-treated PHCs. Further, 8 weeks after implanting PHC-seeded TCP-COL-HA scaffolds subcutaneously in nude mice, we found that miR-193b overexpression strongly enhanced in vivo cartilage formation compared to that found under control conditions. We also found that patients with OA had lower plasma exosomal miR-193b levels than control subjects.Conclusions: These findings indicate that miR-193b-3p directly targets HDAC3, promotes H3 acetylation, and regulates hMSC chondrogenesis and metabolism in PHCs.

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Section: Discussionmentioning

confidence: 97%

MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3

Meng¹,

Li²,

Zhang³

et al. 2018

Theranostics

112

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“…In addition to MMP-19, miR-193b-3p inhibits iNOS in human chondrocytes. miR-193b-3p promotes chondrogenic differentiation of hMSCs but is reduced in OA and in IL-1β-treated chondrocytes (53,54). Increasing miR-193b-3p expression may inhibit degradation of ECM components and moderate inflammation through regulation of iNOS (54).…”

Section: Mirs Involved In Cartilage-protective Mechanismsmentioning

confidence: 99%

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

et al. 2018

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The disabling degenerative disease osteoarthritis (OA) is prevalent among the global population. Articular cartilage degeneration is a central feature of OA; therefore, a better understanding of the mechanisms that maintain cartilage homeostasis is vital for developing effective therapeutic interventions. MicroRNAs (miRs) modulate cell signaling pathways and various processes in articular cartilage via posttranscriptional repression of target genes. As dysregulated miRs frequently alter the homeostasis of articular cartilage, modulating select miRs presents a potential therapeutic opportunity for OA. Here, we review key miRs that have been shown to modulate cartilage-protective or -destructive mechanisms and signaling pathways. Additionally, we use an integrative computational biology approach to provide insight into predicted miR gene targets that may contribute to OA pathogenesis, and highlight the complexity of miR signaling in OA by generating both unique and overlapping gene targets of miRs that mediate protective or destructive effects. Early OA detection would enable effective prevention; thus, miRs are being explored as diagnostic biomarkers. We discuss these ongoing efforts and the applicability of miR mimics and antisense inhibitors as potential OA therapeutics.

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“…Ramp3 is a receptor activitymodifying protein that is highly expressed during joint in ammation [83]. Cyp1b1 (a member of the cytochrome P450 enzyme family), Pcsk1n (an inhibitor of prohormone convertase 1), Dlx3 (a family member of homeobox proteins), Nkd2 (a regulator of in ammatory response), Mmp19 (a subtype of matrix metalloproteinases), Htra4 (a subtype of serine proteases), Aplnr (a G protein-coupled receptor of apelin), Tubb2b (a beta isoform of tubulin), Arg1 (a cytosolic manganese-dependent enzyme) and Clic5 (a chloride intracellular channel protein) are reported to be highly expressed under osteoarthritic condition [84][85][86][87][88][89][90][91][92][93]. Thus, these results suggest that DAE play a potential role in preventing articular cartilage degeneration and in ammation by inhibiting multiple genes involved in the pathophysiology of osteoarthritis.…”

Section: Discussionmentioning

confidence: 99%

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

Yao¹,

Zhou²,

Zhang³

et al. 2020

Preprint

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Background Deer antler is considered as a precious traditional Chinese medicinal material, and has been widely used to reinforce kidney’s yang, nourish essence and strengthen bone function. The most prominent bioactive components in deer antler are water-soluble proteins that play potential roles in bone formation and repair. The aim of this study was to explore the molecular control and therapeutic targets of deer antler extract (DAE) on articular cartilage. Methods DAE was prepared as previously described. All rats were randomly divided into Blank group and DAE group (10 rats per group) after 7-day adaptive feeding. The rats in DAE group were orally administrated with DAE at a dose of 0.2 g/kg per day for 3 weeks and the rats in Blank group were fed with drinking water. Total RNA was isolated from the articular cartilage of knee joints. RNA sequencing (RNA-seq) experiment combined with quantitative real-time polymerase chain reaction (qRT-PCR) verification assay were carried out to explore the molecular control and therapeutic targets of DAE on articular cartilage. Results We demonstrated that DAE played a potential role in promoting cartilage formation, growth and repair, and inhibiting cartilage degeneration and inflammation. These effects were possibly achieved by accelerating the expression of functional genes involved in chondrocyte commitment, survival, proliferation and differentiation, and suppressing the expression of susceptibility genes involved in the pathophysiology of osteoarthritis. Conclusions DAE might serve as a chondroprotective agent for treating cartilage degeneration and inflammation by boosting the ability of cartilage growth and repair. Thus, our findings will contribute towards deepening the knowledge about the molecular control and therapeutic targets of DAE on the treatment of osteoarthritis.

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MicroRNA‐193b‐3p regulates matrix metalloproteinase 19 expression in interleukin‐1β‐induced human chondrocytes

Cited by 31 publications

References 34 publications

MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3

MicroRNA-193b-3p regulates chondrogenesis and chondrocyte metabolism by targeting HDAC3

The complex landscape of microRNAs in articular cartilage: biology, pathology, and therapeutic targets

Insights Into the Molecular Mechanism of Deer Antler Extract Serving as a Potential Chondroprotective Agent for Articular Cartilage

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