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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn 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]
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Biological Functions of miR-29b Contribute to Positive Regulation of Osteoblast Differentiation
Li, Z., Hassan, M. Q., Jafferji, M., Aqeilan, R. I., Garzon, R., Croce, C. M., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809787200 · Cited by 595
Self-citationA microRNA signature for a BMP2-induced osteoblast lineage commitment program
Li, Z., Hassan, M. Q., Volinia, S., van Wijnen, A. J., Stein, J. L., Croce, C. M., Lian, J. B., & Stein, G. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804438105 · Cited by 554
Self-citationNetworks and hubs for the transcriptional control of osteoblastogenesis
Lian, J. B., Stein, G. S., Javed, A., van Wijnen, A. J., Stein, J. L., Montecino, M. A., Hassan, M. Q., Gaur, T., Lengner, C. J., & Young, D. W. (2006) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-006-9001-5 · Cited by 473
Self-citationLi, H., Xie, H., Liu, W., Hu, R., Huang, B., Tan, Y., Liao, E.-Y., Xu, K., Sheng, Z., Zhou, H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39832 · Cited by 464
Retinal and choroidal neovascularization
Campochiaro, P. A. (2000) · Journal of Cellular Physiology · doi:10.1002/1097-4652(200009)184:3 · Cited by 393
Self-citationTranscriptional Control of Skeletogenesis
Karsenty, G. (2008) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.9.081307.164437 · Cited by 390
Suppression of cell growth and invasion by miR-205 in breast cancer
Wu, H., Zhu, S., & Mo, Y. (2009) · Cell Research · doi:10.1038/cr.2009.18 · Cited by 362
Hassan, M. Q., Gordon, J. A. R., Beloti, M. M., Croce, C. M., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007698107 · Cited by 351
Self-citationMir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells
Yu, F., Deng, H., Yao, H., Liu, Q., Su, F., & Song, E. (2010) · Oncogene · doi:10.1038/onc.2010.167 · Cited by 304
Akech, J., Wixted, J. J., Bedard, K., van der Deen, M., Hussain, S., Guise, T. A., van Wijnen, A. J., Stein, J. L., Languino, L. R., Altieri, D. C., et al. (2009) · Oncogene · doi:10.1038/onc.2009.389 · Cited by 302
Self-citationA microRNA regulatory mechanism of osteoblast differentiation
Inose, H., Ochi, H., Kimura, A., Fujita, K., Xu, R., Sato, S., Iwasaki, M., Sunamura, S., Takeuchi, Y., Fukumoto, S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909311106 · Cited by 301
Xu, J., Li, C., Li, Y.-S., Lv, J., Ma, Y., Shao, T.-T., Xu, L., Wang, Y.-Y., Du, L., Zhang, Y. P., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq832 · Cited by 280
Self-citationRegulatory Role of mir-203 in Prostate Cancer Progression and Metastasis
Saini, S., Majid, S., Yamamura, S., Tabatabai, L., Suh, S. O., Shahryari, V., Chen, Y., Deng, G., Tanaka, Y., & Dahiya, R. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2619 · Cited by 276
Fibroblast growth factor signaling controlling osteoblast differentiation
Marie, P. J. (2003) · Gene · doi:10.1016/s0378-1119(03)00748-0 · Cited by 274
Geoffroy, V., Kneissel, M., Fournier, B., BOYDE, A., & Matthias, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.17.6222-6233.2002 · Cited by 263
Hassan, M. Q., Tare, R. S., Lee, S. H., Mandeville, M., Morasso, M. I., Javed, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604508200 · Cited by 221
Self-citationItoh, T., Nozawa, Y., & Akao, Y. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014001 · Cited by 192
Oskowitz, A., Lü, J., Penfornis, P., Ylöstalo, J., McBride, J., Flemington, E. K., Prockop, D. J., & Pochampally, R. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809807105 · Cited by 183
1,25-(OH)2-Vitamin D3 Suppresses the Bone-Related Runx2/Cbfa1 Gene Promoter
Drissi, H. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5474 · Cited by 173
HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genes
Hassan, M. Q., Tare, R. S., Lee, S. H., Mandeville, M., Weiner, B., Montecino, M. A., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01544-06 · Cited by 168
Self-citationJun, J. H., Yoon, W.-J., Seo, S.-B., Woo, K.-M., Kim, G.-S., Ryoo, H.-M., & Baek, J.-H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142307 · Cited by 167
Gaur, T., Hussain, S., Mudhasani, R., Parulkar, I., Colby, J. L., Frederick, D., Kream, B. E., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.01.008 · Cited by 156
Self-citationSelvamurugan, N., Kwok, S., Alliston, T. N., Reiß, M., & Partridge, N. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314048200 · Cited by 119
A Runx2 threshold for the cleidocranial dysplasia phenotype
Lou, Y., Javed, A., Hussain, S., Colby, J. M., Frederick, D., Pratap, J., Xie, R., Gaur, T., van Wijnen, A. J., Jones, S. N., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn383 · Cited by 105
Self-citationMetastatic bone disease: Role of transcription factors and future targets
Pratap, J., Lian, J. B., & Stein, G. S. (2010) · Bone · doi:10.1016/j.bone.2010.05.035 · Cited by 99
Self-citationZhang, Y., Hassan, M. Q., Xie, R., Hawse, J. R., Spelsberg, T. C., Montecino, M. A., Stein, J. L., Lian, J. B., van Wijnen, A. J., & Stein, G. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807466200 · Cited by 81
Self-citationNuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function
Pawlicki, J. M., & STEITZ, J. A. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.10.004 · Cited by 80
Signals that determine the fate of osteoblastic cells.
Frajese, G. V., Martino, M. U. D., Calcagni, E., Pastore, R., Caprio, M., Bultrini, A., Moretti, C., Frajese, G., & Fabbri, A. (2005) · PubMed · Cited by 58
Zhang, Y., Hassan, M. Q., Li, Z., Stein, J. L., Lian, J. B., van Wijnen, A. J., & Stein, G. S. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21844 · Cited by 55
Self-citationInterdependent regulation of p53 and miR-34a in chronic lymphocytic leukemia
Merkel, O., Asslaber, D., Pinon, J., Egle, A., & Greil, R. (2010) · Cell Cycle · doi:10.4161/cc.9.14.12267 · Cited by 50
Zhang, Y., Lian, J. B., Stein, J. L., van Wijnen, A. J., & Stein, G. S. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22299 · Cited by 41
Self-citationZinc finger protein 521, a new player in bone formation
Hesse, E., Kiviranta, R., Wu, M., Saito, H., Yamana, K., Correa, D., Atfi, A., & Baron, R. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05347.x · Cited by 38
Parathyroid Hormone Stimulation of Noncanonical Wnt Signaling in Bone
Bergenstock, M., & Partridge, N. C. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1402.047 · Cited by 33
Cruzat, F., Henríquez, B., Villagra, A., Hepp, M. I., Lian, J. B., van Wijnen, A. J., Stein, J. L., Imbalzano, A. N., Stein, G. S., & Montecino, M. A. (2009) · Biochemistry · doi:10.1021/bi9004792 · Cited by 24
Self-citation1285 REGULATORY ROLE OF MIR-203 IN PROSTATE CANCER PROGRESSION AND METASTASIS
Saini, S., Majid, S., Yamamura, S., Tabatabai, Z. L., Shahryari, V., Deng, G., Tanaka, Y., Carroll, P. R., & Dahiya, R. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.02.971 · Cited by 23
Sierra, O. L., & Towler, D. A. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0029 · Cited by 23
Stein, G. S., Zaidi, S. K., Stein, J. L., Lian, J. B., van Wijnen, A. J., Montecino, M. A., Young, D. W., Javed, A., Pratap, J., Choi, J., et al. (2009) · Biochemistry and Cell Biology · doi:10.1139/o08-094 · Cited by 20
Self-citation
Cited by
Sorted by citations
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
MicroRNA control of bone formation and homeostasis
Lian, J. B., Stein, G. S., van Wijnen, A. J., Stein, J. L., Hassan, M. Q., Gaur, T., & Zhang, Y. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.234 · Cited by 595
Self-citationOsteoblast and osteocyte: Games without frontiers
Capulli, M., Paone, R., & Rucci, N. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.05.003 · Cited by 413
Runx2: Structure, function, and phosphorylation in osteoblast differentiation
Vimalraj, S., Balasubramanian, A., Miranda, P. J., & Selvamurugan, N. (2015) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2015.04.008 · Cited by 393
Iantomasi, T., Romagnoli, C., Palmini, G., Donati, S., Falsetti, I., Miglietta, F., Aurilia, C., Marini, F., Giusti, F., & Brandi, M. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043772 · Cited by 395
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
