title: Mohawk promotes the tenogenesis of mesenchymal stem cells through activation of the TGFβ signaling pathway.
abstract: The transcription factor Mohawk (Mkx) is expressed in developing tendons and is an important regulator of tenogenic differentiation. However, the exact roles of Mkx in tendinopathy and tendon repair remain unclear. Using gene expression Omnibus datasets and immunofluorescence assays, we found that Mkx expression level was dramatically lower in human tendinopathy tissue and it is activated at specific stages of tendon development. In mesenchymal stem cells (MSCs), ectopic Mkx expression strikingly promoted tenogenesis more efficiently than Scleraxis (Scx), a well-known master transcription factor of tendon. Significantly higher levels of tenogenic gene expression and collagen fibril growth were observed with Mkx versus Scx. Interestingly, it was observed that Mkx dramatically upregulated Scx through binding to the Tgfb2 promoter. Additionally, the transplantation of Mkx-expressing-MSC sheets promoted tendon repair in a mouse model of Achilles-tendon defect. Taken together, these data shed light on previously unrecognized roles of Mkx in tendinopathy, tenogenesis, and tendon repair as well as in regulating the TGFβ pathway.
authors.affiliation: Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, People's Republic of China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Shouan
authors.initials: S
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Gong
authors.forename: Ziwang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hu
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D038081:Organogenesis; D015398:Signal Transduction; D052256:Tendinopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013710:Tendons / Q000378:metabolism* / Q000473:pathology; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D053781:Transforming Growth Factor beta2; C000595223:MKX protein, human; C093504:SCX protein, human; C503815:Scx protein, mouse; C509041:TGFB2 protein, human; C509042:Tgfb2 protein, mouse; C510657:mohawk protein, mouse
keywords: Differentiation; Mesenchymal stem cells; Mohawk; TGF-ß; Tendon