MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation

Mao, Guping; Zhang, Z.; Huang, Zhiyu; Chen, Wei; Huang, Guangxin; Meng, Fangang; Kang, Yan

doi:10.1016/j.joca.2016.11.006

Cited by 103 publications

(122 citation statements)

References 40 publications

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“…In this study, we investigated miRNAs that are expressed in a differentiation-dependent pattern in hMSCs and articular chondrocytes. The combination of our previous research [27] and present results revealed that both miR-92a-3p and ADAMTS-4/5 have opposing expression patterns during the chondrogenic differentiation of hMSCs, especially during the late stage of chondrogenic differentiation, and that miR-92a-3p regulates ADAMTS-4/5 expression during chondrogenesis. We also demonstrated changes in the expression of miR-92a-3p in the cartilage of OA patients and in response to IL-1β stimulation.…”

Section: Discussionsupporting

confidence: 84%

“…Specifically, in our previous study [27], when hMSCs were induced to differentiate into chondrocytes, miR-92a-3p expression was upregulated, especially during the early stage of chondrogenesis (days 14-21), but was subsequently down-regulated during hypertrophy and endochondral ossification (days 21-35) [27]. This expression pattern was quite similar to that of miR-140, which has been shown to stimulate chondrogenesis in vitro.…”

Section: Discussionmentioning

confidence: 56%

“…MiR-92a expression decreases rapidly in macrophages upon stimulation with Toll-like receptor ligands, and miR-92a controls the inflammatory response by targeting the MKK4/JNK/c-Jun pathway [41]. In our previous studies, we demonstrated that miR-92a-3p plays an important role in both cartilage development and degeneration via directly targeting HDAC2, and that siHDAC2 can also repress the expression of ADAMTS-4/5 in primary human chondrocytes [26,27].…”

Section: Discussionmentioning

confidence: 98%

“…We also observed the rapid up-regulation of miR-92a-3p in chondrogenic human mesenchymal stem cells (hMSCs) beginning on day 7, which peaked at 21 days and was followed by a marked decrease in expression levels at day 28 [27]. In addition, the expression level of miR-92a-3p was significantly reduced in OA cartilage compared with that detected in normal cartilage [27]. In a luciferase reporter assay, we demonstrated that histone deacetylase 2 (HDAC2) was the target of miR-92a-3p [27].…”

Section: Introductionmentioning

confidence: 83%

“…In addition, the expression level of miR-92a-3p was significantly reduced in OA cartilage compared with that detected in normal cartilage [27]. In a luciferase reporter assay, we demonstrated that histone deacetylase 2 (HDAC2) was the target of miR-92a-3p [27]. However, using miRNA target prediction algorithms, we discovered that ADAMTS-4 and ADAMTS-5 may be potential targets of miR-92a-3p.…”

Section: Introductionmentioning

confidence: 90%

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MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Mao¹,

Zhang²,

Zhang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). Methods: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. Results: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3′-UTR of human ADAMTS-4/5 mRNA.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 90%

See 3 more Smart Citations

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Mao¹,

Zhang²,

Zhang³

et al. 2017

Cell Physiol Biochem

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Lithium‐Containing Biomaterials Stimulate Cartilage Repair through Bone Marrow Stromal Cells‐Derived Exosomal miR‐455‐3p and Histone H3 Acetylation

Liu

Chen

et al. 2023

Adv Healthcare Materials

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The repair of damaged cartilage still remains a great challenge in clinic. It is demonstrated that bone marrow stromal cells (BMSCs)‐chondrocytes communication is of great significance for cartilage repair. Moreover, BMSCs have been confirmed to enhance biological function of chondrocytes via exosome‐mediated paracrine pathway. Lithium‐containing scaffolds have been reported to effectively promote cartilage regeneration; however, whether lithium‐containing biomaterial could facilitate cartilage regeneration through regulating BMSCs‐derived exosomes has not been illustrated. In the study, the model lithium‐substituted bioglass ceramic (Li‐BGC) is selected and regulatory effects of BMSCs‐derived exosomes after Li‐BGC treatment (Li‐BGC‐Exo) are systemically evaluated. The data reveal that Li‐BGC‐Exo notably promotes chondrogenesis, which attributes to the upregulated exosomal miR‐455‐3p transfer, consequently leads to suppression of histone deacetylase 2 (HDAC2) and enhanced histone H3 acetylation in chondrocytes. Notably, BMSCs‐derived exosomes after LiCl treatment (LiCl‐Exo) exhibits the similar regulatory effect with Li‐BGC‐Exo, indicating that the pro‐chondrogenesis capability of them is mainly owing to the lithium ions. Furthermore, the in vivo study proves that LiCl‐Exo remarkably facilitates cartilage regeneration. The research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by lithium‐containing biomaterials, and suggests that application of lithium‐containing scaffolds may be a promising strategy for cartilage regeneration.

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Mesenchymal Stem Cell‐Derived Exosomes for Effective Cartilage Tissue Repair and Treatment of Osteoarthritis

Kim

Choi

Kim

2020

Biotechnology Journal

120

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Osteoarthritis (OA) is one of the most common musculoskeletal diseases, caused by cellular inflammatory responses and subsequent structural disruption in osteochondral extracellular matrix (ECM) in cartilage tissues. Various cell-therapies have been recently developed via the exogenous administration of mesenchymal stem cells (MSCs) due to their intrinsic regenerative capacity of self-renewal and chondrogenic differentiation. However, MSC-based cellular approaches have exhibited some technical limitations including dedifferentiation during MSC expansion, reduction of regenerative efficacy upon administration, and inconsistent quality control in large-scale cell production. To overcome these disadvantages, exosome mediated cartilage tissue regeneration has been investigated. Since exosome derived from MSC (MSC-exosome) transport and deliver multiple cellular components from their original MSC sources, they could be utilized as alternative therapeutic agents for OA treatment. Recent studies have shown that the administration of MSC-exosome effectively reduced a production of inflammatory cytokines in chondrocytes, increased the expression of cartilage ECM component, and eventually augment cartilage tissue regeneration in a series of in vivo studies. Therefore, this review emphasizes current engineering approaches via MSC-exosome for cartilage tissue repair, as a functional OA treatment technique.

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MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation

Abstract: Our results suggest that miR-92a-3p regulates cartilage development and homeostasis, which directly targets HDAC2, indicating histone hyperacetylation plays an important role in increased expression of cartilage matrix.

Cited by 103 publications

References 40 publications

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Lithium‐Containing Biomaterials Stimulate Cartilage Repair through Bone Marrow Stromal Cells‐Derived Exosomal miR‐455‐3p and Histone H3 Acetylation

Mesenchymal Stem Cell‐Derived Exosomes for Effective Cartilage Tissue Repair and Treatment of Osteoarthritis

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