ArticleMolecular metabolism2016
Myocardin-related transcription factor A (MRTFA) regulates the fate of bone marrow mesenchymal stem cells and its absence in mice leads to osteopenia.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
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- Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling.Annals of translational medicine · 2023Article
- Mechanosensation mediates volume adaptation of cardiac cells and spheroids in 3D.Materials today. Bio · 2022Article
- Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification.Stem cell reports · 2022Article
- Attenuated clinical and osteoclastic phenotypes of Paget's disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene.BMC medical genomics · 2022Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Steering cell behavior through mechanobiology in 3D: A regenerative medicine perspective.Biomaterials · 2021Review
- Skeletal glucocorticoid signalling determines leptin resistance and obesity in aging mice.Molecular metabolism · 2020Article
- Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.Journal of orthopaedic surgery and research · 2020Article
- F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiONanoscale research letters · 2020Article
- Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases.Frontiers in cell and developmental biology · 2020Review
- Mechanosensing of Mechanical Confinement by Mesenchymal-Like Cells.Frontiers in physiology · 2020Review
- Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells.Stem cells international · 2020Article
- Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling.Frontiers in cell and developmental biology · 2020Article
- Myocardin-Related Transcription Factor A Promotes Recruitment of ITGA5+ Profibrotic Progenitors during Obesity-Induced Adipose Tissue Fibrosis.Cell reports · 2018Article
- Cell-Matrix Interactions and Matricrine Signaling in the Pathogenesis of Vascular Calcification.Frontiers in cardiovascular medicine · 2018Review
- Review
- TGF-β1 regulates the expression and transcriptional activity of TAZ protein via a Smad3-independent, myocardin-related transcription factor-mediated mechanism.The Journal of biological chemistry · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveArising from common progenitors in the bone marrow, adipogenesis and osteogenesis are closely associated yet mutually exclusive during bone marrow mesenchymal stem cell (BMSC) development. Previous studies have shown that morphological changes can affect the early commitment of pluripotent BMSCs to the adipose versus osteoblastic lineage via modulation of RhoA activity. The RhoA pathway regulates actin polymerization to promote the incorporation of globular actin (G-actin) into filamentous actin (F-actin). In doing so, myocardin-related transcription factors (MRTFs) dissociate from bound G-actin and enter the nucleus to co-activate serum response factor (SRF) target gene expression. In this study, we investigated whether MRTFA/SRF is acting downstream of the RhoA pathway to regulate BMSC commitment in mice.
methodsThe effects of knocking out MRTFA on skeletal homeostasis was studied in MRTFA KO mice using micro-CT, QPCR and western blot assays. To determine how MRTFA affects the mechanisms regulating BMSC fate decisions, primary bone marrow stromal cells from WT and MRTFA KO mice as well as C3H10T1/2 cell lines were analyzed in vitro.
resultsGlobal MRTFA KO mice have lower whole body weight, shorter femoral and tibial lengths as well as significantly decreased bone mass in their femurs. BMSCs isolated from the KO mice show increased adipogenesis and reduced osteogenesis when compared to WT littermates. KO mice, particularly females, develop osteopenia with age, and this was enhanced by a high fat diet. Over-expression of MRTFA or SRF enhances osteogenesis in CH310T1/2 cell lines. Sca1(+), CD45(-) cells from KO marrow express lower amounts of smooth muscle actin (SMA) and TAZ/YAP target genes compared to WT counterparts.
conclusionThis study identified MRTFA as a novel regulator of skeletal homeostasis by regulating the balance between adipogenic and osteogenic differentiation of BMSCs. We propose that MRTFA promotes the osteogenic activity of TAZ/YAP by maintaining SMA production in BMSCs.
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