The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways

Zhou, You Lang; Liu, Siyu; Wang, Wei; Sun, Qiang; Lv, Mengzhu; Yang, Shude; Tong, S. Y.; Guo, Shu

doi:10.1186/s13287-020-02117-4

Cited by 22 publications

(14 citation statements)

References 43 publications

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“…During chondrogenic differentiation, we observed reduced levels of beta catenin, whose degradation is promoted by SOX9 [34], as well as reduced p-ERK levels, whose activation has been demonstrated to repress chondrocytic commitment [35]. Recently, it has been demonstrated that miR-204 blocks ERK pathway activation [36] and that the miR-204-5p/FOXC1/GDF7 axis regulates osteogenic differentiation [16]. Therefore, these findings, in combination with the inverse modulation between miR-204 and pERK observed in our study, suggest that miR-204 can affect the differentiation process by modulating important cellular signaling pathways.…”

Section: Discussionmentioning

confidence: 75%

“…miR-204 is also involved in different pathological processes by targeting important biological pathways [12][13][14][15]. AKT and p38 as well as BMP2/Runx2/ALP signaling pathways are affected by miR 204 expression during osteogenesis [16,17]. In addition, miR-204 has been reported to be involved in cartilage inflammation, fractures and bone-related diseases [18].…”

Section: Introductionmentioning

confidence: 99%

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Modulation of miR-204 Expression during Chondrogenesis

Carbonare

Bertacco

Minoia

et al. 2022

IJMS

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RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes’ maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes’ maturation.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Modulation of miR-204 Expression during Chondrogenesis

Carbonare

Bertacco

Minoia

et al. 2022

IJMS

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“…By qRT‐PCR, we demonstrated downregulation of lncSLCO1C1 significantly reduced the expression of FOXC1 and AP1S2 (Figure S6L ), all of which are downstream targets of miR‐211‐5p/miR‐204‐5p. 24 , 25 In addition, in vitro experiments showed upregulation by transfection of either miR‐211‐5p mimic or miR‐204‐5p mimic significantly reduced cell proliferation and metastasis of SGC7901 (Figure S7A–E ) and BGC823 (Figure S7F–J ). Downregulation of either miR‐211‐5p or miR‐204‐5p abolished the effect on decreased cell proliferation, migration and invasion of SGC7901 (Figure S7K–M ) and BGC823 (Figure S7P–T ) by downregulation of lncSLCO1C1 expression.…”

Section: Resultsmentioning

confidence: 96%

“…By qRT-PCR, we demonstrated downregulation of lncSLCO1C1 significantly reduced the expression of FOXC1 and AP1S2 (Figure S6L), all of which are downstream targets of miR-211-5p/miR-204-5p. 24,25 In addition, in vitro experiments showed upregulation by transfection of either miR-211-5p mimic or miR-204-5p mimic significantly reduced cell proliferation and metastasis of SGC7901 (Figure S7A-E…”

Section: Lncslco1c1 Increases Ssrp1 Expression By Adsorbing Mir-211-5...mentioning

confidence: 99%

Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy

Xiao

Liu

et al. 2022

Clinical & Translational Med

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Background Gastric carcinoma (GC) is one of the most deadly diseases due to tumour metastasis and resistance to therapy. Understanding the molecular mechanism of tumour progression and drug resistance will improve therapeutic efficacy and develop novel intervention strategies. Methods Differentially expressed long non‐coding RNAs (lncRNAs) in clinical specimens were identified by LncRNA microarrays and validated in different clinical cohorts by quantitative real‐time polymerase chain reaction (qRT‐PCR), in situ hybridisation and bioinformatics analysis. Biological functions of lncRNA were investigated by using cell proliferation assays, migration assays, xenograft tumour models and bioinformatics analysis. Effects of lncSLCO1C1 on GC cell survival were assessed by comet assays and immunofluorescence assays. Underlying molecular mechanisms were further explored by using a number of technologies including RNA pull‐down, mass spectrometry analysis, RNA immunoprecipitation, co‐immunoprecipitation, miRNA sequencing, luciferase reporter assays and molecular modelling. Results LncSLCO1C1 was highly upregulated in GC tissue samples and associated with GC patients’ poor overall survival. Overexpression of lncSLCO1C1 promoted proliferation and migration, whereas decreased lncSLCO1C1 expression produced the opposite effects. lncSLCO1C1 also mediated tumour resistance to chemotherapy with oxaliplatin by reducing DNA damage and increasing cell proliferation. Despite sequence overlapping between lncSLCO1C1 and PDE3A, alternations of PDE3A expression had no effect on the GC cell progression, indicating that lncSLCO1C1, not PDE3A, related with the progression of GC cells. Mechanistically, lncSLCO1C1 serves as a scaffold for the structure‐specific recognition protein 1 (SSRP1)/H2A/H2B complex and regulates the function of SSRP1 in reducing DNA damage. Meanwhile, lncSLCO1C1 functions as a sponge to adsorb miR‐204‐5p and miR‐211‐5p that target SSRP1 mRNA, and thus increases SSRP1 expression. Patients with high expressions of both lncSLCO1C1 and SSRP1 have poor overall survival, highlighting the role of lncSLCO1C1 in GC progression. Conclusions LncSLCO1C1 promotes GC progression by enhancing cell growth and preventing DNA damage via interacting and scaffolding the SSRP1/H2A/H2b complex and absorbing both miR‐211‐5p and miR‐204‐5p to increase SSRP1 expression.

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“…44,45 Akt is the crucial stimulus for osteogenesis. 27,28,46,47 Also, maxillofacial bone regeneration could be promoted via the PTEN/PI3K/Akt/HIF-1α pathway. In the present study, the protein level of Akt was found to be improved after treatment by RvD1 (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Impact of Resolvin D1 on the inflammatory phenotype of periodontal ligament cell response to hypoxia

Cai

Liu

Jing

et al. 2022

J of Periodontal Research

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Objective: Periodontal ligament cells (PDLCs) are critical for wound healing and regenerative capacity of periodontal diseases. Within an inflammatory periodontal pocket, a hypoxic environment can aggravate periodontal inflammation, where PDLCs response to the inflammation would change. Resolvin D1 (RvD1) is an endogenous lipid mediator, which can impact intracellular inflammatory pathways of periodontal/oral cells and periodontal regeneration. It is not clear how hypoxia and RvD1 impact the inflammatory responses of pro-inflammatory PDLCs phenotype. Therefore, this study aimed to test hypoxia could induce changes in pro-inflammatory phenotype of PDLCs and RvD1 could reverse it. Methods: Human PDLCs were cultured from periodontal tissues from eight healthy individuals and were characterized by immunofluorescence staining of vimentin and cytokeratin. Cell viability was examined by Methyl-thiazolyl-tetrazolium (MTT) assay. To examine the effects of hypoxia and RvD1 on the inflammatory responses of proinflammatory PDLCs phenotype, protein levels and gene expressions of inflammatory cytokines and signal transduction molecules were measured by enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and real-time quantitative reverse transcription PCR (real-time qRT-PCR). Alizarin red S staining and real-time qRT-PCR were employed to study the effects of hypoxia and RvD1 on the osteogenic differentiation of pro-inflammatory PDLCs phenotype. Results: It was found that hypoxia increases the expression of inflammatory factors at the gene level (p < .05). RvD1 reduced the expression of IL-1β (p < .05) in PDLCs under hypoxia both at the protein and RNA levels. There were increases in the expression of p38 mitogen-activated protein kinase (p38 MAPK, p < .01) and protein kinase B (Akt, p < .05) in response to RvD1. Also, a significantly higher density of calcified nodules was observed after treatment with RvD1 for 21 days under hypoxia. Conclusion: Our results indicate that hypoxia up-regulated the inflammatory level of PDLCs. RvD1 can reduce under-hypoxia-induced pro-inflammatory cytokines in the inflammatory phenotype of PDLCs. Moreover, RvD1 promotes the calcium nodules in PDLCs, possibly by affecting the p38 MAPK signaling pathway through Akt and HIF-1α.

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The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways

Cited by 22 publications

References 43 publications

Modulation of miR-204 Expression during Chondrogenesis

Modulation of miR-204 Expression during Chondrogenesis

Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy

Impact of Resolvin D1 on the inflammatory phenotype of periodontal ligament cell response to hypoxia

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