Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system.
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 ScxCreknock-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 ScxCre/CreKI 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 ScxCre/CreKI mice. These results highlighted the functional importance of both transient and persistent expression domains of Scx for proper integration of the musculoskeletal components.
Department of Molecular Biology and Biochemistry, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
Yuki
Y
Yoshimoto
Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Aki
A
Takimoto
Laboratory of Animal Experiment for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Hitomi
H
Watanabe
Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Yuji
Y
Hiraki
Laboratory of Animal Experiment for Regeneration, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Gen
G
Kondoh
Department of Molecular Biology and Biochemistry, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.|Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
Chisa
C
Shukunami
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000473:pathology; D002356:Cartilage / Q000002:abnormalities / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D023061:Gene Order; D018390:Gene Targeting; D017930:Genes, Reporter; D056426:Genetic Loci; D059765:Homologous Recombination; D008022:Ligaments / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D041641:Musculoskeletal Development / Q000235:genetics*; D010766:Phosphorylation; D055758:SOX9 Transcription Factor / Q000235:genetics; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D013710:Tendons / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D055758:SOX9 Transcription Factor; D051785:Smad Proteins; C503815:Scx protein, mouse; C527933:Sox9 protein, mouse