GATA4-activated lncRNA MALAT1 promotes osteogenic differentiation through inhibiting NEDD4-mediated RUNX1 degradation

Huang, Xianzhe; Jie, Shuo; Li, Wenzhao; Liu, Chan

doi:10.1038/s41420-023-01422-0

Cited by 8 publications

(2 citation statements)

References 49 publications

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“…Huang et al 97 examined the effects of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1, a lncRNA that controls the Wnt/β‐catenin axis) and GATA‐binding protein 4 (GATA4, which recognizes the promoter of osteogenic differentiation genes in related BMSCs) on bone metabolism in an older population. GATA4 and MALAT1 expression was identified as downregulated in the bone tissue of 18‐month‐old mice through osteoporosis modeling.…”

Section: Noncoding Rnasmentioning

confidence: 99%

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

Zhong,

Zhou,

Pan

et al. 2024

The FASEB Journal

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Alterations to the human organism that are brought about by aging are comprehensive and detrimental. Of these, an imbalance in bone homeostasis is a major outward manifestation of aging. In older adults, the decreased osteogenic activity of bone marrow mesenchymal stem cells and the inhibition of bone marrow mesenchymal stem cell differentiation lead to decreased bone mass, increased risk of fracture, and impaired bone injury healing. In the past decades, numerous studies have reported the epigenetic alterations that occur during aging, such as decreased core histones, altered DNA methylation patterns, and abnormalities in noncoding RNAs, which ultimately lead to genomic abnormalities and affect the expression of downstream signaling osteoporosis treatment and promoter of fracture healing in older adults. The current review summarizes the impact of epigenetic regulation mechanisms on age‐related bone homeostasis imbalance.

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Section: Noncoding Rnasmentioning

confidence: 99%

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

Zhong,

Zhou,

Pan

et al. 2024

The FASEB Journal

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“…Gata4 is upregulated in the aortic root of Tgfbr1 M318R/+ LDS mice. Based on the analysis described above, and its known role in driving the upregulation of pathways previously involved in aneurysm progression 44,73,80 , Gata4 emerged as a potential molecular determinant of increased risk of dilation of the aortic root in LDS. Although levels of Gata4 mRNA are intrinsically higher in the aortic root relative to the ascending aorta even in control mice (Fig.…”

Section: Expression Of Cluster-defining Transcripts For the Vsmc2 And...mentioning

confidence: 99%

Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Bramel,

Camejo,

Creamer

et al. 2024

Preprint

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Loeys-Dietz syndrome (LDS) is an aneurysm disorder caused by mutations that decrease transforming growth factor-β (TGF-β) signaling. Although aneurysms develop throughout the arterial tree, the aortic root is a site of heightened risk. To identify molecular determinants of this vulnerability, we investigated the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1M318R/+ LDS mice by single cell and spatial transcriptomics. Reduced expression of components of the extracellular matrix-receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human scRNAseq dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired TGF-β signaling.

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Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle

Hosoyama,

Kawai‐Takaishi,

Iida

et al. 2024

J cachexia sarcopenia muscle

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BackgroundRecent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis.MethodsMPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen‐inducible MP‐specific VDR‐deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross‐sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3–4). In addition, a vitamin D‐deficient diet was provided to wild‐type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation.ResultsVitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1‐mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR‐deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil‐Red O+ area). In consistency with in‐vitro findings, VdrMPcKO mice and mice fed a vitamin D‐deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively.ConclusionsVitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

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GATA4-activated lncRNA MALAT1 promotes osteogenic differentiation through inhibiting NEDD4-mediated RUNX1 degradation

Cited by 8 publications

References 49 publications

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

Intrinsic Gata4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model

Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle

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