title: Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.
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.
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.|Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakamichi
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Systems Biomedicine, National Research Institute for Child Health and Development, 2-10-1, Okura Setagaya, Tokyo 157-8535, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inui
authors.affiliation: Department of Systems Biomedicine, National Research Institute for Child Health and Development, 2-10-1, Okura Setagaya, Tokyo 157-8535, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Onizuka
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kayama
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Systems Biomedicine, National Research Institute for Child Health and Development, 2-10-1, Okura Setagaya, Tokyo 157-8535, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Inagawa
authors.affiliation: Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-161, La Jolla, California 92037, USA.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Lotz
authors.affiliation: Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1143, Japan.
authors.forename: Daisuke
authors.identifier: 0000-0003-4189-9270
authors.initials: D
authors.lastname: Sakai
authors.affiliation: University of California, San Diego, 9500 Gilman Dr Mail Code 0863, La Jolla, California 92093-0863, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Department of Systems Biomedicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.|Department of Systems Biomedicine, National Research Institute for Child Health and Development, 2-10-1, Okura Setagaya, Tokyo 157-8535, Japan.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-161, La Jolla, California 92037, USA.|CREST from Japan Agency for Medical Research and Development, 1-7-1 Ootemachi, Tiyoda, Tokyo 100-0004, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asahara
mesh_terms: D000328:Adult; D000818:Animals; D000070616:Annulus Fibrosus / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D012038:Regeneration; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C000595223:MKX protein, human; C510657:mohawk protein, mouse