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1.
Cell Prolif ; 57(6): e13607, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38353178

RESUMO

To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. It was showed that there was an m6A methylation site in 3'UTR of FBLN1 mRNA, and the mutation of the m6A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m6A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR-615-3p negatively regulated FBLN1 by binding FBLN1 3'UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC-mediated bone regeneration. Then, we discovered miR-615-3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m6A-miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615-3p mediated the decay of FBLN1 mRNA which facilitated by m6A reading protein YTHDF2. This provided a novel m6A-miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais , MicroRNAs , Osteogênese , Proteínas de Ligação a RNA , Cordão Umbilical , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese/genética , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Cordão Umbilical/citologia , Cordão Umbilical/metabolismo , Regiões 3' não Traduzidas , Animais , Células Cultivadas , Regeneração Óssea/genética , Estabilidade de RNA , Adenosina/análogos & derivados
2.
Int J Oral Sci ; 15(1): 48, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852994

RESUMO

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), ßIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.


Assuntos
Leucemia , Células-Tronco Mesenquimais , Animais , Humanos , Ratos , Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Neurogênese , Células-Tronco , Fatores de Transcrição HES-1/metabolismo
3.
Int J Mol Sci ; 24(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37445785

RESUMO

Stem cells from the apical papilla (SCAPs) are used to regulate the microenvironment of nerve defects. KDM6B, which functions as an H3K27me3 demethylase, is known to play a crucial role in neurogenesis. However, the mechanism by which KDM6B influences the neurogenesis potential of SCAPs remains unclear. We evaluated the expression of neural markers in SCAPs by using real-time RT-PCR and immunofluorescence staining. To assess the effectiveness of SCAP transplantation in the SCI model, we used the BBB scale to evaluate motor function. Additionally, toluidine blue staining and Immunofluorescence staining of NCAM, NEFM, ß-III-tubulin, and Nestin were used to assess nerve tissue remodeling. Further analysis was conducted through Microarray analysis and ChIP assay to study the molecular mechanisms. Our results show that KDM6B inhibits the expression of NeuroD, TH, ß-III tubulin, and Nestin. In vivo studies indicate that the SCAP-KDM6Bsh group is highly effective in restoring spinal cord structure and motor function in rats suffering from SCI. Our findings suggest that KDM6B directly binds to the HES1 promoter via regulating H3K27me3 and HES1 expression. In conclusion, our study can help understand the regulatory role of KDM6B in neurogenesis and provide more effective treatments for nerve injury.


Assuntos
Histonas , Tubulina (Proteína) , Ratos , Animais , Histonas/metabolismo , Nestina/genética , Nestina/metabolismo , Diferenciação Celular , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Células-Tronco/metabolismo , Neurogênese , Papila Dentária/metabolismo , Células Cultivadas , Osteogênese
4.
Front Cell Dev Biol ; 9: 721205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589487

RESUMO

Objective: Articular cartilage injury is common and difficult to treat clinically because of the characteristics of the cartilage. Bone marrow-derived mesenchymal stem cell (BMSC)-mediated cartilage regeneration is a promising therapy for treating articular cartilage injury. BMSC differentiation is controlled by numerous molecules and signaling pathways in the microenvironment at both the transcriptional and post-transcriptional levels. However, the possible function of super enhancer long non-coding RNAs (SE-lncRNAs) in the chondrogenic differentiation of BMSCs is still unclear. Our intention was to explore the expression profile of SE-lncRNAs and potential target genes regulated by SE-lncRNAs during chondrogenic differentiation in BMSCs. Materials and Methods: In this study, we conducted a human Super-Enhancer LncRNA Microarray to investigate the differential expression profile of SE-lncRNAs and mRNAs during chondrogenic differentiation of BMSCs. Subsequent bioinformatic analysis was performed to clarify the important signaling pathways, SE-lncRNAs, and mRNAs associated with SE-lncRNAs regulating the chondrogenic differentiation of BMSCs. Results: A total of 77 SE-lncRNAs were identified, of which 47 were upregulated and 30 were downregulated during chondrogenic differentiation. A total of 308 mRNAs were identified, of which 245 were upregulated and 63 were downregulated. Some pathways, such as focal adhesion, extracellular matrix (ECM)-receptor interaction, transforming growth factor-ß (TGF-ß) signaling pathway, and PI3K-Akt signaling pathway, were identified as the key pathways that may be implicated in the chondrogenic differentiation of BMSCs. Moreover, five potentially core regulatory mRNAs (PMEPA1, ENC1, TES, CDK6, and ADIRF) and 37 SE-lncRNAs in chondrogenic differentiation were identified by bioinformatic analysis. Conclusion: We assessed the differential expression levels of SE-lncRNAs and mRNAs, along with the chondrogenic differentiation of BMSCs. By analyzing the interactions and co-expression, we identified the core SE-lncRNAs and mRNAs acting as regulators of the chondrogenic differentiation potential of BMSCs. Our study also provided novel insights into the mechanism of BMSC chondrogenic and cartilage regeneration.

5.
Int J Clin Pract ; 75(10): e14537, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34132007

RESUMO

OBJECTIVE: To examine the association between hip and knee osteoarthritis (OA) and falls. Potentially relevant articles that examine the association between hip, knee, radiological, and self-reported OA and falls were retrieved from PubMed, EMBASE, Scopus, and Web of Science up until March of 2020. METHODS: The pooled risk ratios (RRs) as well as their related 95% confidence intervals (CIs) were calculated. Statistic and subgroup analyses were performed. A total of 21 studies involving 146 965 participants were included. RESULTS: No association was found between hip OA and falls. The pooled RRs value suggested a higher prevalence of falls in knee OA patients (RR = 1.35, 95% CI: 1.20 to 1.51, P < .00001) and self-reported OA (RR = 1.33, 95% CI: 1.23 to 1.45, P < .00001) than in non-OA subjects. The pooled RR value suggested no difference between prevalence of falls in radiological OA patients compared to non-OA subjects (RR = 1.82, 95% CI: 0.89 to 3.73, P = .10). Both radiological and self-reported knee OA seem to be positively associated with falls, while no obvious association was found between hip OA and falls. CONCLUSIONS: Therefore, knee OA is a risk factor for falls which should be closely monitored.


Assuntos
Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Prevalência , Fatores de Risco
6.
Orthop J Sports Med ; 9(12): 23259671211063844, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34988238

RESUMO

BACKGROUND: It is unclear whether coracoacromial ligament release during the Latarjet procedure will increase superior translation of the shoulder joint. PURPOSE: To evaluate whether a modified suture button Latarjet procedure can decrease the acromiohumeral distance (AHD). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective analysis was conducted among 155 patients who underwent a modified suture button Latarjet procedure between 2013 and 2015. AHD was measured on bilateral computed tomography scans taken preoperatively and on scans of the affected shoulder taken on postoperative day 1 and postoperative month (POM) 6, POM 36, and POM 60. At each time point, we recorded pain on a visual analog scale (VAS) and objective shoulder function using the American Shoulder and Elbow Surgeons, Rowe, and Walch-Duplay scores. Preoperative and final follow-up VAS and functional scores were compared using the paired t test. Pairwise comparison of AHD values at each follow-up time point were compared with the preoperative intact side using the paired t test. Intra- and interobserver reproducibility of the AHD measurements was evaluated using the intraclass correlation coefficient. RESULTS: A total of 104 patients who met the criteria completed the final follow-up, which occurred at 62.6 ± 2.4 months (mean ± SD). When compared with presurgery, the VAS and all functional scores improved significantly at the last follow-up (P < .001 for all). Intra- and interobserver intraclass correlation coefficients indicated good reliability for the ADH measurements. Preoperatively, there were no differences in AHD values between the intact and affected shoulders (7.8 ± 0.8 mm for both; P = .851). The AHD values at postoperative day 1 and POM 6, POM 36, and POM 60 were 9.6 ± 0.7 mm, 8.6 ± 0.9 mm, 8.0 ± 0.8 mm, and 7.9 ± 0.8 mm, respectively, all of which were larger than those of the preoperative intact side (P < .001 for all). CONCLUSION: The modified suture button Latarjet procedure not only offered satisfactory therapeutic effects but also did not decrease the AHD at 5-year follow-up.

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