Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs
| Autor: | Tomohiro Kayama, Koichi Masuda, Shizuko Ichinose, Hiroshi Asahara, Masafumi Inui, Naoko Onizuka, Kensuke Kataoka, Masaki Mori, Hidetsugu Suzuki, Toshifumi Ozaki, Martin Lotz, Yoshiaki Ito, Daisuke Sakai, Ryo Nakamichi, Masayo Inagawa |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male General Physics and Astronomy Regenerative Medicine Inbred C57BL Pathogenesis Mice 2.1 Biological and endogenous factors Aetiology Intervertebral Disc Cells Cultured Regulation of gene expression Mice Knockout Mice Inbred C3H Multidisciplinary Cultured Mesenchymal Stromal Cells Anatomy Middle Aged musculoskeletal system Inbred C3H Cell biology medicine.anatomical_structure Female musculoskeletal diseases Adult 1.1 Normal biological development and functioning Science Cells Knockout Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Young Adult Underpinning research medicine Genetics Animals Humans Regeneration Transcription factor Homeodomain Proteins Regeneration (biology) Mesenchymal stem cell Wild type Annulus Fibrosus Intervertebral disc Mesenchymal Stem Cells General Chemistry Stem Cell Research Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Musculoskeletal Homeobox |
| Zdroj: | Nature communications, vol 7, iss 1 Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016) Nature Communications |
| Popis: | 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. Homeobox protein Mohwak (Mkx) is involved in tendon and ligament development. Here the authors show that Mkx in the outer annulus fibrosus of the intervertebral disc plays a role in maintenance of the IVD, showing that stem cells overexpressing Mkx enhance therapeutic IVD regeneration in mice. |
| Databáze: | OpenAIRE |
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