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Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR‐29b‐3p and activating TGF‐β1 signaling
Author(s) -
Lu Ying-Fei,
Liu Yang,
Fu Wei-Ming,
Xu Jia,
Wang Bin,
Sun Yu-Xin,
Wu Tian-Yi,
Xu Liang-Liang,
Chan Kai-Ming,
Zhang Jin-Fang,
Li Gang
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600722r
Subject(s) - microbiology and biotechnology , tendon , transforming growth factor , regeneration (biology) , microrna , regulator , cancer research , long non coding rna , downregulation and upregulation , signal transduction , cellular differentiation , biology , chemistry , gene , anatomy , genetics
Tendon 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‐b1‐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‐β1 and type I collagen, thereby forming a novel regulatory feedback loop between H19 and TGF‐b1 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‐β1 signaling. Regulation of the TGF‐β1/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‐β1 signaling. FASEB J. 31, 954–964 (2017). www.fasebj.org