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The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1

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Zhang, Jin, Tu, Qisheng, Bonewald, Lynda F, He, Xi, Stein, Gary, Lian, Jane, Chen, Jake·2011·Journal of Bone and Mineral Research

Abstract

Dickkopf-related protein 1 (DKK1) is essential to maintain skeletal homeostasis as an inhibitor of Wnt signaling and osteogenic differentiation. The purpose of this study was to investigate the molecular mechanisms underlying the developmental stage–specific regulation of the DKK1 protein level. We performed a series of studies including luciferase reporter assays, micro-RNA microarray, site-specific mutations, and gain- and loss-of-function analyses. We found that the DKK1 protein level was regulated via DKK1 3' UTR by miRNA control, which was restricted to osteoblast-lineage cells. As a result of decreased DKK1 protein level by miR-335-5p, Wnt signaling was enhanced, as indicated by elevated GSK-3β phosphorylation and increased β-catenin transcriptional activity. The effects of miR-335-5p were reversed by anti-miR-335-5p treatment, which downregulated endogenous miR-335-5p. In vivo studies showed high expression levels of miR-335-5p in osteoblasts and hypertrophic chondrocytes of mouse embryos, indicating a pivotal role of miR-335-5p in regulating bone development. In conclusion, miR-335-5p activates Wnt signaling and promotes osteogenic differentiation by downregulating DKK1. This cell- and development-specific regulation is essential and mandatory for the initiation and progression of osteogenic differentiation. miR-335-5p proves to be a potential and useful targeting molecule for promoting bone formation and regeneration. © 2011 American Society for Bone and Mineral Research

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Metadata

Authors
Zhang, J., Tu, Q., Bonewald, L. F., He, X., Stein, G., Lian, J., & Chen, J.
Venue
Journal of Bone and Mineral Research
Published
2011-02-23
Volume
26
Issue
8
Pages
1953-1963
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
OpenAlex
W2095004208
Cited by
289
References
9
FWCI
5.89
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. https://app.cochat.ai/papers/10.1002/jbmr.377
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Zhang, J., Tu, Q., Bonewald, L. F., He, X., Stein, G., Lian, J., & Chen, J. (2011). Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.377

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