Transcription factor mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

Koji Otabe, Hiroyuki Nakahara, Akihiko Hasegawa, Tetsuya Matsukawa, Fumiaki Ayabe, Naoko Onizuka, Masafumi Inui, Shuji Takada, Yoshiaki Ito, Ichiro Sekiya, Takeshi Muneta, Martin Lotz, Hiroshi Asahara

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Orthopaedic Research
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Keywords

  • Mesenchymal stem cells
  • Mohawk
  • Scleraxis
  • Tenogenesis

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