ArticleStem cells (Dayton, Ohio)2019
A Reciprocal Role of the Smad4-Taz Axis in Osteogenesis and Adipogenesis of Mesenchymal Stem Cells.
Article in Stem cells (Dayton, Ohio), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation.Stem cell reports · 2026Article
- LATS1/2 Inhibitor Attenuates Osteoclast Differentiation via Hippo-YAP/TAZ Signaling Pathway and Alleviates Osteoporosis in Ovariectomized Rats.Current medical science · 2026Article
- Transcriptional control of PPP2CB by YAP1 and TEAD1 mediates AMPK inhibition and mTORC1 activation in vascular smooth muscle cells.iScience · 2026Article
- When Bone Forms Where It Shouldn't: Heterotopic Ossification in Muscle Injury and Disease.International journal of molecular sciences · 2025Review
- Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices.International journal of molecular sciences · 2025Article
- Review
- Review
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- Emerging role and function of Hippo-YAP/TAZ signaling pathway in musculoskeletal disorders.Stem cell research & therapy · 2024Review
- S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling.Experimental and therapeutic medicine · 2024Article
- Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1.Biological research · 2024Article
- Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: Therapeutic implications in bone defect repair.Genes & diseases · 2023Review
- Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis.Frontiers in cell and developmental biology · 2023Review
- Pulsed Electromagnetic Field Promotes Bone Anabolism in Postmenopausal Osteoporosis through the miR-6976/BMP/Smad4 Axis.Journal of tissue engineering and regenerative medicine · 2023Article
- Transit Amplifying Cells (TACs): a still not fully understood cell population.Frontiers in bioengineering and biotechnology · 2023Review
- A body map of super-enhancers and their function in pig.Frontiers in veterinary science · 2023Article
- OLMALINC/OCT4/BMP2 axis enhances osteogenic-like phenotype of renal interstitial fibroblasts to participate in Randall's plaque formation.Molecular medicine (Cambridge, Mass.) · 2022Article
- Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells.World journal of stem cells · 2022Article
- Yap and Taz promote osteogenesis and prevent chondrogenesis in neural crest cells in vitro and in vivo.Science signaling · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into mature cells of various cell types. Although the differentiation process of MSCs requires lineage-specific transcription factors, the exact molecular mechanism that determines MSCs differentiation is not clearly addressed. Here, we demonstrate a Smad4-Taz axis as a new intrinsic regulator for adipo-osteogenic differentiation of MSCs and show that this function of Smad4 is independent of the transforming growth factor-β signal. Smad4 directly bound to the Taz protein and facilitated nuclear localization of Taz through its nuclear localization signal. Nuclear retention of Taz by direct binding to Smad4 increased expression of osteogenic genes through enhancing Taz-runt-related transcription factor 2 (Runx2) interactions in the C3H10T1/2 MSC cell line and preosteoblastic MC3T3-E1 cells, whereas it suppressed expression of adipogenic genes through promoting Taz-peroxisome proliferator-activated receptor-γ (PPARγ) interaction in C3H10T1/2 and preadipogenic 3T3-L1 cells. A reciprocal role of the Smad4 in osteogenic and adipogenic differentiation was also observed in human adipose tissue-derived stem cells (hASCs). Consequently, Smad4 depletion in C3H10T1/2 and hASCs reduced nuclear retention of Taz and thus caused the decreased interaction with Runx2 or PPARγ, resulting in delayed osteogenesis or enhanced adipogenesis of the MSC. Therefore, these findings provide insight into a novel function of Smad4 to regulate the balance of MSC lineage commitment through reciprocal targeting of the Taz protein in osteogenic and adipogenic differentiation pathways. Stem Cells 2019;37:368-381.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.