FGF-2 Stimulates the Growth of Tenogenic Progenitor Cells to Facilitate the Generation of <i>Tenomodulin</i>-Positive Tenocytes in a Rat Rotator Cuff Healing Model

Tokunaga, Takuya; Shukunami, Chisa; Okamoto, Naoya; Taniwaki, Takuya; Oka, Kiyoshi; Sakamoto, Hidetoshi; Ide, Junji; Mizuta, Hiroshi; Hiraki, Yuji

doi:10.1177/0363546515597488

Cited by 108 publications

(128 citation statements)

References 28 publications

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“…In skin, Tnmd expression significantly downregulated between day 1 and 3 after skin incision, while in the tendon defect studies Tnmd expression significantly upregulated in the period between 1-2 weeks in the patella and between 4-12 weeks in the rotator cuff that was FGF -2 treated (Kameyama et al 2015, Omachi et al 2015, Tokunaga et al 2015). This data strongly motivates further investigations on the exact roles of Tnmd in tissue repair.…”

Section: Tenomodulinmentioning

confidence: 96%

TENOgenic MODULating INsider factor: systematic assessment on the functions of tenomodulin gene

Dex

Lin

Shukunami

et al. 2016

Gene

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Tenomodulin (TNMD, Tnmd) is a gene highly expressed in tendon known to be important for tendon maturation with key implications for the residing tendon stem/progenitor cells as well as for the regulation of endothelial cell migration in chordae tendineae cordis in the heart and in experimental tumour models. This review aims at providing an encompassing overview of this gene and its protein. In addition, its known expression pattern as well as putative signalling pathways will be described. A chronological overview of the discovered functions of this gene in tendon and other tissues and cells is provided as well as its use as a tendon and ligament lineage marker is assessed in detail and discussed. Last, information about the possible connections between TNMD genomic mutations and mRNA expression to various diseases is delivered. Taken together this review offers a solid synopsis on the up-to-date information available about TNMD and aids at directing and focusing the future research to fully uncover the roles and implications of this interesting gene.

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Section: Tenomodulinmentioning

confidence: 96%

TENOgenic MODULating INsider factor: systematic assessment on the functions of tenomodulin gene

Dex

Lin

Shukunami

et al. 2016

Gene

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“…The syndetome is a scleraxis (Scx)-positive subdomain that occupies the dorsolateral portion of the sclerotome to form the axial skeleton [12]. Scx also marks the progenitor cells of tendons and ligaments in the appendicular and craniofacial regions [5], [13], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization and function of tenomodulin, a marker of tendons and ligaments that integrate musculoskeletal components

Shukunami

Yoshimoto

Takimoto

et al. 2016

Japanese Dental Science Review

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SummaryTendons and ligaments are dense fibrous bands of connective tissue that integrate musculoskeletal components in vertebrates. Tendons connect skeletal muscles to the bone and function as mechanical force transmitters, whereas ligaments bind adjacent bones together to stabilize joints and restrict unwanted joint movement. Fibroblasts residing in tendons and ligaments are called tenocytes and ligamentocytes, respectively. Tenomodulin (Tnmd) is a type II transmembrane glycoprotein that is expressed at high levels in tenocytes and ligamentocytes, and is also present in periodontal ligament cells and tendon stem/progenitor cells. Tnmd is related to chondromodulin-1 (Chm1), a cartilage-derived angiogenesis inhibitor, and both Tnmd and Chm1 are expressed in the CD31− avascular mesenchyme. The conserved C-terminal hydrophobic domain of these proteins, which is characterized by the eight Cys residues to form four disulfide bonds, may have an anti-angiogenic function. This review highlights the molecular characterization and function of Tnmd, a specific marker of tendons and ligaments.

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“…Cellular adhesion in the periodontal ligament is decreased on loss of Tnmd and enhanced on Tnmd overexpression17. In a rat rotator cuff healing model, fibroblast growth factor-2 enhanced tendon-to-bone healing, in which Tnmd expression was associated with formation of aligned collagen fibres in the repair tissue18. Loss of Tnmd results in reduced self-renewal and augmented senescence of tendon stem/progenitor cells19.…”

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confidence: 99%

Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system

Yoshimoto

Takimoto

Watanabe

et al. 2017

Sci Rep

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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 ScxCre 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 ScxCre/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 ScxCre/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.

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FGF-2 Stimulates the Growth of Tenogenic Progenitor Cells to Facilitate the Generation of Tenomodulin-Positive Tenocytes in a Rat Rotator Cuff Healing Model

Abstract: These findings provide clues regarding the clinical development of regenerative repair strategies for RC injury.

Cited by 108 publications

References 28 publications

TENOgenic MODULating INsider factor: systematic assessment on the functions of tenomodulin gene

TENOgenic MODULating INsider factor: systematic assessment on the functions of tenomodulin gene

Molecular characterization and function of tenomodulin, a marker of tendons and ligaments that integrate musculoskeletal components

Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system

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