The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Overexpression of MiR-335-5p Promotes Bone Formation and Regeneration in Mice
Abstract
MicroRNAs (miRNAs) and the Wnt signaling pathway play critical roles in regulating bone development and homeostasis. Our previous study revealed high expression of miR-335-5p in osteoblasts and hypertrophic chondrocytes in mouse embryos and the ability of miR-335-5p to promote osteogenic differentiation by downregulating Wnt antagonist Dickkopf-1 (DKK1). The purpose of this study was to investigate the effects of miR-335-5p constitutive overexpression on bone formation and regeneration in vivo. To that end, we generated a transgenic mouse line specifically overexpressing miR-335-5p in osteoblasts lineage by the osterix promoter and characterized its bone phenotype. Bone histomorphometry and μCT analysis revealed higher bone mass and increased parameters of bone formation in transgenic mice than in wild-type littermates. Increased bone mass in transgenic mice bones also correlated with enhanced expression of osteogenic differentiation markers. Upon osteogenic induction, bone marrow stromal cells (BMSCs) isolated from transgenic mice displayed higher mRNA expression of osteogenic markers than wild-type mice BMSCs cultures. Protein expression of Runx2 and Osx was also upregulated in BMSC cultures of transgenic mice upon osteogenic induction, whereas that of DKK1 was downregulated. Most important, BMSCs from transgenic mice were able to repair craniofacial bone defects as shown by μCT analysis, H&E staining, and osteocalcin (OCN) immunohistochemistry of newly formed bone in defects treated with BMSCs. Taken together, our results demonstrate constitutive overexpression of miR-335-5p driven by an osterix promoter in the osteoblast lineage induces osteogenic differentiation and bone formation in mice and support the potential application of miR-335-5p–modified BMSCs in craniofacial bone regeneration. © 2017 American Society for Bone and Mineral Research.
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?
In the citing paper
“Canonical Wnt signaling is involved as a major mechanism in the control of osteogenesis and bone mass accrual by many regulators such as BMPs, nuclear factor-I (NFI) family members and microRNAs [31–36].”
From N-myc downstream regulated gene 1 suppresses osteoblast differentiation through inactivating Wnt/β-catenin signaling (2022) · cites this paper as [35]
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
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., & Lifton, R. P. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa013444 · Cited by 1,591
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
Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., et al. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200201089 · Cited by 1,086
Flagged first, then by citations
Research works printed but not linked: 32
- Gong, 2001, LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development, Cell, 107, 513, 10.1016/S0092-8674(01)00571-2 · DOI · Paper page
- Bennett, 2005, Regulation of osteoblastogenesis and bone mass by Wnt10b, Proc Natl Acad Sci U S A, 102, 3324, 10.1073/pnas.0408742102 · DOI
- Day, 2005, Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis, Dev Cell, 8, 739, 10.1016/j.devcel.2005.03.016 · DOI · Paper page
- Hill, 2005, Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes, Dev Cell, 8, 727, 10.1016/j.devcel.2005.02.013 · DOI
- Rodda, 2006, Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors, Development, 133, 3231, 10.1242/dev.02480 · DOI
- Rawadi, 2003, BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop, J Bone Miner Res, 18, 1842, 10.1359/jbmr.2003.18.10.1842 · DOI
- Zhang, 2008, Inhibition of Wnt signaling by the osteoblast-specific transcription factor Osterix, Proc Natl Acad Sci U S A, 105, 6936, 10.1073/pnas.0710831105 · DOI
- van der Horst, 2005, Downregulation of Wnt signaling by increased expression of Dickkopf-1 and -2 is a prerequisite for late-stage osteoblast differentiation of KS483 cells, J Bone Miner Res, 20, 1867, 10.1359/JBMR.050614 · DOI
- Gaur, 2010, Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse, Dev Biol, 340, 10, 10.1016/j.ydbio.2010.01.008 · DOI
- Bae, 2012, miRNA-34c regulates Notch signaling during bone development, Hum Mol Genet, 21, 2991, 10.1093/hmg/dds129 · DOI
- Eskildsen, 2011, MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo, Proc Natl Acad Sci U S A, 108, 6139, 10.1073/pnas.1016758108 · DOI
- Inose, 2009, A microRNA regulatory mechanism of osteoblast differentiation, Proc Natl Acad Sci U S A, 106, 20794, 10.1073/pnas.0909311106 · DOI
- Kim, 2012, miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1, J Bone Miner Res, 27, 1669, 10.1002/jbmr.1604 · DOI
- Li, 2009, A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans, J Clin Invest, 119, 3666, 10.1172/JCI39832 · DOI
- Li, 2009, Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation, J Biol Chem, 284, 15676, 10.1074/jbc.M809787200 · DOI
- Glinka, 1998, Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction, Nature, 391, 357, 10.1038/34848 · DOI · Paper page
- MacDonald, 2004, Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6, Development, 131, 2543, 10.1242/dev.01126 · DOI
- MacDonald, 2007, Bone mass is inversely proportional to Dkk1 levels in mice, Bone, 41, 331, 10.1016/j.bone.2007.05.009 · DOI
- Zhang, 2011, Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1, J Bone Miner Res, 26, 1953, 10.1002/jbmr.377 · DOI
- Tome, 2011, miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells, Cell Death Differ, 18, 985, 10.1038/cdd.2010.167 · DOI
- Lin, 2014, MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is regulated through two positive feedback loops, J Bone Miner Res, 29, 1575, 10.1002/jbmr.2163 · DOI
- Tu, 2011, Adiponectin inhibits osteoclastogenesis and bone resorption via APPL1-mediated suppression of Akt1, J Biol Chem, 286, 12542, 10.1074/jbc.M110.152405 · DOI
- Chen, 1996, Expression of rat bone sialoprotein promoter in transgenic mice, J Bone Miner Res, 11, 654, 10.1002/jbmr.5650110513 · DOI
- Valverde, 2008, Overexpression of bone sialoprotein leads to an uncoupling of bone formation and bone resorption in mice, J Bone Miner Res, 23, 1775, 10.1359/jbmr.080605 · DOI
- Yu, 2015, Adiponectin regulates bone marrow mesenchymal stem cell niche through a unique signal transduction pathway: an approach for treating bone disease in diabetes, Stem Cells, 33, 240, 10.1002/stem.1844 · DOI
- Tu, 2006, Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells, Biochem Biophys Res Commun, 341, 1257, 10.1016/j.bbrc.2006.01.092 · DOI
- Tu, 2008, Haploinsufficiency of Runx2 results in bone formation decrease and different BSP expression pattern changes in two transgenic mouse models, J Cell Physiol, 217, 40, 10.1002/jcp.21472 · DOI
- Ye, 2011, Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs, Biomaterials, 32, 5065, 10.1016/j.biomaterials.2011.03.053 · DOI
- Morvan, 2006, Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass, J Bone Miner Res, 21, 934, 10.1359/jbmr.060311 · DOI
- Hu, 2005, Sequential roles of Hedgehog and Wnt signaling in osteoblast development, Development, 132, 49, 10.1242/dev.01564 · DOI · Paper page
- Wahlquist, 2014, Inhibition of miR-25 improves cardiac contractility in the failing heart, Nature, 508, 531, 10.1038/nature13073 · DOI
- Tu, 2007, Osterix overexpression in mesenchymal stem cells stimulates healing of critical-sized defects in murine calvarial bone, Tissue engineering, 13, 2431, 10.1089/ten.2006.0406 · DOI
Cited by
Sorted by citations
Shi, X., Cen, Y., Shan, L., Tian, L., Zhu, E., Yuan, H., Li, X., Liu, Y., & Wang, B. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02714-5 · Cited by 15
Metadata
- Authors
- Zhang, L., Tang, Y., Zhu, X., Tu, T., Sui, L., Han, Q., Yu, L., Meng, S., Zheng, L., Valverde, P., Tang, J., Murray, D., Zhou, X., Drissi, H., Dard, M. M., Tu, Q., & Chen, J.
- Affiliations
- Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduSichuanChina
- Division of Oral BiologyTufts University School of Dental MedicineBostonMAUSA
- Department of Orthopaedic SurgeryUniversity of ConnecticutFarmingtonCTUSA
- Periodontology and Implant DentistryNew York University College of DentistryNew YorkNYUSA
- Department of Anatomy and Cell BiologyTufts University School of MedicineSackler School of Graduate Biomedical SciencesBostonMAUSA
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-07-29
- Volume
- 32
- Issue
- 12
- Pages
- 2466-2475
- ISSN
- 0884-0431
- 1523-4681
- PMC
- PMC5732062
- Cited by
- 106
- References
- 3
- Language
- en
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Funders
- National Institutes of Health (R01DE021464, R01DE025681)
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
