Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs

Ryo Nakamichi, Yoshiaki Ito, Masafumi Inui, Naoko Onizuka, Tomohiro Kayama, Kensuke Kataoka, Hidetsugu Suzuki, Masaki Mori, Masayo Inagawa, Shizuko Ichinose, Martin K. Lotz, Daisuke Sakai, Koichi Masuda, Toshifumi Ozaki and Hiroshi Asahara ()
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Ryo Nakamichi: Tokyo Medical and Dental University
Yoshiaki Ito: Tokyo Medical and Dental University
Masafumi Inui: National Research Institute for Child Health and Development
Naoko Onizuka: National Research Institute for Child Health and Development
Tomohiro Kayama: Tokyo Medical and Dental University
Kensuke Kataoka: Tokyo Medical and Dental University
Hidetsugu Suzuki: Tokyo Medical and Dental University
Masaki Mori: Tokyo Medical and Dental University
Masayo Inagawa: National Research Institute for Child Health and Development
Shizuko Ichinose: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University
Martin K. Lotz: The Scripps Research Institute
Daisuke Sakai: Surgical Science, Tokai University School of Medicine
Koichi Masuda: University of California, San Diego
Toshifumi Ozaki: Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Hiroshi Asahara: Tokyo Medical and Dental University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx−/− mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration.

Date: 2016
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DOI: 10.1038/ncomms12503

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