title: Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-β1 signaling.
abstract: 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-β1-induced tenogenic differentiationin vitroand 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-β1 to mediate tenogenic differentiation. Our study demonstrated that H19 promotes tenogenic differentiation bothin vitroandin vivoby 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.
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ying-Fei
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhouv, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Fu
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.|Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Sun
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Xu
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; and.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chan
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; zhangjf06@cuhk.edu.hk.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; and.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; gangli@cuhk.edu.hk.|Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; and.|Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; C094335:H19 long non-coding RNA; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D053773:Transforming Growth Factor beta1
keywords: lncRNA; miRNA; pathway; tendon differentiation