Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-beta 1 signaling
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AbstractTendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration. In this study, we found that lncRNA H19 stimulated tenogenesis of human tendon-derived stem cells. Stable overexpression of H19 significantly accelerated TGF-beta 1-induced tenogenic differentiation in vitro and accelerated tendon healing in a mouse tendon defect model. H19 directly targeted miR-29b-3p, which is considered to be a negative regulator of tenogenesis. Furthermore, miR-29b-3p directly suppressed the expression of TGF-beta 1 and type I collagen, thereby forming a novel regulatory feedback loop between H19 and TGF-beta 1 to mediate tenogenic differentiation. Our study demonstrated that H19 promotes tenogenic differentiation both in vitro and in vivo by targeting miR-29b-3p and activating TGF-beta 1 signaling. Regulation of the TGF-beta 1/H19/miR-29b-3p regulatory loop may be a new strategy for treating tendon injury.-Lu, Y.-F., Liu, Y., Fu, W.-M., Xu, J., Wang, B., Sun, Y.-X., Wu, T.-Y., Xu, L.-L, Chan, K.-M., Zhang, J.-F., Li, G. Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-beta 1 signaling.
All Author(s) ListLu YF, Liu Y, Fu WM, Xu J, Wang B, Sun YX, Wu TY, Xu LL, Chan KM, Zhang JF, Li G
Journal nameFASEB Journal
Year2017
Month3
Volume Number31
Issue Number3
PublisherFEDERATION AMER SOC EXP BIOL
Pages954 - 964
ISSN0892-6638
eISSN1530-6860
LanguagesEnglish-United Kingdom
Keywordstendon differentiation, pathway, lncRNA, miRNA
Web of Science Subject CategoriesBiochemistry & Molecular Biology;Biology;Cell Biology;Biochemistry & Molecular Biology;Life Sciences & Biomedicine - Other Topics;Cell Biology

Last updated on 2020-06-07 at 00:36