title: Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.
abstract: Mohawk homeobox (MKX) has been demonstrated as a tendon/ligament specific transcription factor. The aim of this study was to investigate the role of MKX in ligament/tenogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs). Human BMMSCs were treated with 50 ng/ml BMP-12 or transduced with MKX or scleraxis (SCX) adenoviral vector. Gene expression analysis was performed by quantitative reverse transcribed polymerase chain reaction (qRT-PCR). Rat BMMSCs were seeded in a collagen scaffold and transplanted into a rat Achilles tendon defect model. Tenogenesis related gene expressions and histological features were analyzed. BMP-12 induced tenogenesis in BMMSCs as indicated by increased COL1a1, TNXB, DCN and SCX mRNA, and MKX expression increased simultaneously. Rat BMMSCs enhanced defect repair and were still detectable 3 weeks after transplantation. Increased expressions of COL1a1, TNC and TNMD in vivo were also correlated with upregulated MKX. Adenoviral MKX promoted expression of COL1a1, TNXB, and TNMD in BMMSCs. This study demonstrated that MKX gene expression is enhanced during the tenogenic differentiation of BMMSCs in vitro and in vivo, and the adenoviral overexpression of MKX increases tendon extracellular matrix gene expression and protein production. Thus, MKX is a key factor for tenogenic differentiation of MSCs.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-161, La Jolla, 92037, California; Department of System Biomedicine, National Research Institute for Child Health and Development, Tokyo, Japan; Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakahara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ayabe
authors.forename: Naoko
authors.initials: N
authors.lastname: Onizuka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inui
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
authors.forename: Martin
authors.initials: M
authors.lastname: Lotz
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
mesh_terms: D000125:Achilles Tendon / Q000293:injuries; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D055412:Growth Differentiation Factors / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D019063:Tenascin / Q000378:metabolism; D013710:Tendons / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
chemical_list: D019485:Bone Morphogenetic Proteins; D003094:Collagen; D058575:Decorin; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D019063:Tenascin; D014157:Transcription Factors; C546878:DCN protein, human; C499470:GDF7 protein, human; C000595223:MKX protein, human; C422444:TNMD protein, human; C081865:tenascin X
keywords: Mesenchymal stem cells; Mohawk; Scleraxis; tenogenesis