Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

Sun, Lingtong; Ma, Jianfei; Cheng, Juan; Pan, Zhijun; Li, Lijun

doi:10.3389/fmolb.2022.800288

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…Recently, researches about AOX1's function in MSCs came out, suggesting its function in the regulation and induction of MSCs towards osteogenesis and adipogenesis. Firstly, there was bioinformatic analysis suggested its potential in osteogenic differentiation in hMSCs, identi ed AOX1 as a potential regulator of osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs) 14 . Furthermore, research in hMSCs revealed that AOX1 silencing induced by miR-513a-5p enhances osteogenic proliferation and differentiation 15 .…”

Section: Discussionmentioning

confidence: 99%

“…10 And some of the pathways, such as retinol 11,12 and serotonin 13 pathway, has reported to be associated with the osteogenesis and/or adipogenesis of MSCs. AOX1's relevance in mesenchymal stem cells has garnered attention in current researches, indicating its potential in osteoblastic genes upregulation and alkaline phosphatase (ALP) activity enhancement 14,15 .…”

Section: Introductionmentioning

confidence: 99%

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Positive Impact of AOX1 on RXR Signaling Leads to Inhibition of Osteogenesis in hPDLMSCs

Sun,

Iwata

2024

Preprint

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Alveolar bone loss resulting from periodontal disease ultimately leads to tooth loss. Periodontal ligament mesenchymal stem cells (PDLMSCs) serve as the tissue-specific cells responsible for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. In this study, we explored the role of aldehyde oxidase 1 (AOX1) in regulating the osteoinduction of human periodontal ligament stem cells (hPDLMSCs). hPDLMSCs were isolated from clinically healthy donors, and AOX1 expression was assessed by comparing inducted and non-inducted hPDLMSCs. Remarkably, we observed a significant upregulation of AOX1 expression during osteoinduction, while AOX1 silencing resulted in the enhanced osteogenic potential of hPDLMSCs. Subsequent experiments and analysis unveiled the involvement of retinoid X receptor (RXR) signaling in the inhibition of osteogenesis in hPDLMSCs. Ligands targeting the RXR receptor mirrored the effects of AOX1 on osteogenesis, as evidenced by alterations in alkaline phosphatase (ALP) activity and bone formation levels. Collectively, these findings underscore the potential regulatory role of AOX1 via RXR signaling in the osteogenesis of hPDLMSCs. This elucidation is pivotal for advancing hPDLMSCs-based periodontal regeneration strategies and lays the groundwork for the development of targeted therapeutic interventions aimed at enhancing bone formation in the context of periodontal disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Positive Impact of AOX1 on RXR Signaling Leads to Inhibition of Osteogenesis in hPDLMSCs

Sun,

Iwata

2024

Preprint

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“…The level of AOX1 in differentiated bone marrow-derived mesenchymal stem cells was higher and gradually increased. Overexpression of AOX1 significantly increased the expression of osteo-specific genes, which clearly indicated that AOX1 plays an important role in osteogenic differentiation [ 29 ]. Oncology studies have shown that regulation of ACTC1 is associated with cancer invasion, migration, and patient prognosis [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of abnormal methylation modification differential expression mRNAs between low-grade and high-grade intervertebral disc degeneration and its correlation with immune cells

Xie,

Zhang,

Liu

2024

Annals of Medicine

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Background Intervertebral disc degeneration (IDD) is an important cause of low back pain. The aim of this study is to identify the potential molecular mechanism of abnormal methylation-modified DNA in the progression of IDD, hoping to contribute to the diagnosis and management of IDD. Methods Low-grade IDD (grade I–II) and high-grade IDD (grade III–V) data were downloaded from GSE70362 and GSE129789 datasets. The abnormally methylated modified differentially expressed mRNAs (DEmRNAs) were identified by differential expression analysis (screening criteria were p < .05 and |logFC| > 1) and differential methylation analysis (screening criteria were p < .05 and |δβ| > 0.1). The classification models were constructed, and the receiver operating characteristic analysis was also carried out. In addition, functional enrichment analysis and immune correlation analysis were performed and the miRNAs targeted for the abnormally methylated DEmRNAs were predicted. Finally, expression validation was performed using real-time PCR. Results Compared with low-grade IDD, seven abnormal methylation-modified DEmRNAs (AOX1, IBSP, QDPR, ABLIM1, CRISPLD2, ACTC1 and EMILIN1) were identified in high-grade IDD, and the classification models of random forests (RF) and support vector machine (SVM) were constructed. Moreover, seven abnormal methylation-modified DEmRNAs and classification models have high diagnostic accuracy (area under the curve [AUC] > 0.8). We also found that AUC values of single abnormal methylation-modified DEmRNA were all lower than those of RF and SVM classification models. Pearson correlation analysis found that macrophages M2 and EMILIN1 had significant negative correlation, while macrophages M2 and IBSP had significant positive correlation. In addition, four targeted relationship pairs (hsa-miR-4728-5p-QDPR, hsa-miR-4533-ABLIM1, hsa-miR-4728-5p-ABLIM1 and hsa-miR-4534-CRISPLD2) and multiple signalling pathways (for example, PI3K-AKT signalling pathway, osteoclast differentiation and calcium signalling pathway) were also identified that may be involved in the progression of IDD. Conclusion The identification of abnormal methylation-modified DEmRNAs and the construction of classification models in this study were helpful for the diagnosis and management of IDD progression.

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“…Osteoblasts differentiate from the mesenchymal stem cells in bone marrow (BMSCs) (Sun et al, 2022). Previous studies have indicated that there are two opposite trends of BMSC differentiation that result from the balance between osteogenesis and adipogenesis (Wang et al, 2022a;Suo et al, 2022).…”

Section: Melatonin Promotes Osteoblast Differentiation and Inhibits O...mentioning

confidence: 99%

The role of melatonin in the development of postmenopausal osteoporosis

Yang

Qiu²,

Cao³

et al. 2022

Front. Pharmacol.

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Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.

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Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells

Cited by 4 publications

References 42 publications

Positive Impact of AOX1 on RXR Signaling Leads to Inhibition of Osteogenesis in hPDLMSCs

Positive Impact of AOX1 on RXR Signaling Leads to Inhibition of Osteogenesis in hPDLMSCs

Comprehensive analysis of abnormal methylation modification differential expression mRNAs between low-grade and high-grade intervertebral disc degeneration and its correlation with immune cells

The role of melatonin in the development of postmenopausal osteoporosis

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