First Author | Yoshimoto Y | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Pages | 45010 | PubMed ID | 28327634 |
Mgi Jnum | J:274387 | Mgi Id | MGI:6296513 |
Doi | 10.1038/srep45010 | Citation | Yoshimoto Y, et al. (2017) Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system. Sci Rep 7:45010 |
abstractText | Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is expressed persistently in tendons/ligaments, but transiently in entheseal cartilage. In this study, we generated a novel Scx(Cre) knock-in (KI) allele, by in-frame replacement of most of Scx exon 1 with Cre recombinase (Cre), to drive Cre expression using Scx promoter and to inactivate the endogenous Scx. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing Scx. Expression of tenomodulin, a marker of mature tenocytes and ligamentocytes, was almost absent in tendons and ligaments of Scx(Cre/Cre) KI mice lacking Scx to indicate defective maturation. In homozygotes, the transiently Scx-expressing entheseal regions such as the rib cage, patella cartilage, and calcaneus were small and defective and cartilaginous tuberosity was missing. Decreased Sox9 expression and phosphorylation of Smad1/5 and Smad3 were also observed in the developing entheseal cartilage, patella, and deltoid tuberosity of Scx(Cre/Cre) KI mice. These results highlighted the functional importance of both transient and persistent expression domains of Scx for proper integration of the musculoskeletal components. |