The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2
Open accessAbstract
Lineage progression in osteoblasts and chondrocytes is stringently controlled by the cell-fate–determining transcription factor Runx2. In this study, we directly addressed whether microRNAs (miRNAs) can control the osteogenic activity of Runx2 and affect osteoblast maturation. A panel of 11 Runx2-targeting miRNAs (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-137, miR-204, miR-205, miR-217, miR-218, and miR-338) is expressed in a lineage-related pattern in mesenchymal cell types. During both osteogenic and chondrogenic differentiation, these miRNAs, in general, are inversely expressed relative to Runx2. Based on 3′UTR luciferase reporter, immunoblot, and mRNA stability assays, each miRNA directly attenuates Runx2 protein accumulation. Runx2-targeting miRNAs differentially inhibit Runx2 protein expression in osteoblasts and chondrocytes and display different efficacies. Thus, cellular context contributes to miRNA-mediated regulation of Runx2. All Runx2-targeting miRNAs (except miR-218) significantly impede osteoblast differentiation, and their effects can be reversed by the corresponding anti-miRNAs. These findings demonstrate that osteoblastogenesis is limited by an elaborate network of functionally tested miRNAs that directly target the osteogenic master regulator Runx2.
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“The experiments in vitro have demonstrated that it can control the progression of osteoblast and chondrocyte lineages and inhibit osteogenic differentiation by targeting the transcription factors Runx2 and Satb2 in mice.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [109]
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“miR-23a is highly expressed in osteoblasts, chondrocytes, and fibroblast cell lines.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [109]
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“there existed no notable variance in the number of osteoblasts and osteoclasts between miR-23 transgenic and wild-type mice, along with their activity in the bone.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [109]
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“In addition, an increase in RANKL/OPG ratio expressed by osteocytes was also observed in connexin43-deficient rats, suggesting that a disruption in cell-to-cell communication between osteocytes may induce the release of local proosteoclastogenic cytokines [33, 196, 197].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [33]
In the citing paper
“In addition, an increase in RANKL/OPG ratio expressed by osteocytes was also observed in connexin43-deficient rats, suggesting that a disruption in cell-to-cell communication between osteocytes may induce the release of local proosteoclastogenic cytokines [33, 196, 197].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [33]
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Cites
Prediction of Mammalian MicroRNA Targets
Lewis, B. P., Shih, I.-H., Jones-Rhoades, M. W., Bartel, D. P., & Burge, C. B. (2003) · Cell · doi:10.1016/s0092-8674(03)01018-3 · Cited by 5,199
Combinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603
John, B., Enright, A. J., Aravin, A., Tuschl, T., Sander, C., & Marks, D. S. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020363 · Cited by 3,796
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608
Small silencing RNAs: an expanding universe
Ghildiyal, M., & Zamore, P. D. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2504 · Cited by 2,418
Miranda, K. C., Huynh, T., Tay, Y., Ang, Y.-S., Tam, W.-L., Thomson, A. M., Lim, B., & Rigoutsos, I. (2006) · Cell · doi:10.1016/j.cell.2006.07.031 · Cited by 2,063
Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A., & Burge, C. B. (2008) · Science · doi:10.1126/science.1155390 · Cited by 1,349
Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
Gaur, T., Lengner, C. J., Hovhannisyan, H., Bhat, R. A., Bodine, P. V. N., Komm, B. S., Javed, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500608200 · Cited by 1,170
Self-citationRegulation of bone development and extracellular matrix protein genes by RUNX2
Komori, T. (2009) · Cell and Tissue Research · doi:10.1007/s00441-009-0832-8 · Cited by 806
MicroRNA-204 Regulates Runx2 Protein Expression and Mesenchymal Progenitor Cell Differentiation
Huang, J. H., Zhao, L., Xing, L., & Chen, D. (2009) · Stem Cells · doi:10.1002/stem.288 · Cited by 607
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Keflee, R. D. (2018) · Universiti Sains Malaysia Institutional Repository (Universiti Sains Malaysia)
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Govindan, R., Kalimuthu, S., Poomarimuthu, M., Jayaraman, S., & Rajasekaran, P. N. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18800-8.00025-3
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Stein, G. S. (2025) · Academia Biology · doi:10.20935/acadbiol7628
Self-citationZhang, Q., Guo, Z., Hu, W., Tang, W., Gao, X., Han, C., Wang, X., Gong, P., & Long, J. (2025) · Experimental Cell Research · doi:10.1016/j.yexcr.2025.114746
Georgi, N. (2013) · doi:10.3990/1.9789036535205
Guo, R., Wu, C., Liu, F., 董天华, & Zhang, T. (2024) · Figshare · doi:10.6084/m9.figshare.26647929
Melnik, S., Gabler, J., Dreher, S. I., Hecht, N., Hofmann, N., Grossner, T. L., & Richter, W. (2020) · Figshare · doi:10.6084/m9.figshare.13364318
Guo, R., Wu, C., Liu, F., 董天华, & Zhang, T. (2024) · Figshare · doi:10.6084/m9.figshare.26647932
Mijovic, M., Čuturilo, G., Stojanovic, J. R., Brankovic, M., Miletić, A., Bosankic, B., Dedovic, M., Perović, D., Maksimović, N., & Damnjanović, T. (2025) · Balkan Journal of Medical Genetics · doi:10.2478/bjmg-2025-00026
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Haseltine, W. A., & Patarca, R. (2026) · Springer eBooks · doi:10.1007/978-3-032-30270-0_5
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Metadata
- Authors
- Zhang, Y., Xie, R.-L., Croce, C. M., Stein, J. L., Lian, J. B., van Wijnen, A. J., & Stein, G. S.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- The Ohio State University (US)
- Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-31
- Volume
- 108
- Issue
- 24
- Pages
- 9863-9868
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3116419
- OpenAlex
- W2028928108
- Cited by
- 423
- References
- 48
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 19 · 2023: 20 · 2022: 15 · 2021: 27 · 2020: 36 · 2019: 42 · 2018: 32 · 2017: 36 · 2016: 35 · 2015: 46 · 2014: 24 · 2013: 42 · 2012: 27
- FWCI
- 12.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA129242, P01CA082834)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049069, R01AR039588)
- National Institute of Dental and Craniofacial Research (R37DE012528)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- microRNA, Runx2, osteogenic differentiation, osteoblasts, chondrogenic differentiation, mesenchymal lineage, microRNA target regulation, miR-218, transcription factor regulation
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Line, Gene Expression Regulation, Luciferases, Osteoblasts, Osteogenesis, RNA, Messenger, Blotting, Western, Cell Lineage, Chondrocytes, 3' Untranslated Regions, Gene Expression Profiling, RNA Stability, MicroRNAs, NIH 3T3 Cells, Core Binding Factor Alpha 1 Subunit, Mice
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