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Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon.

Kayama T, Mori M, Ito Y, Matsushima T, Nakamichi R, Suzuki H, Ichinose S, Saito M, Marumo K, Asahara H - Mol. Cell. Biol. (2016)

Bottom Line: In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover.Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation.Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.

No MeSH data available.


Mechanical loading induces Mkx and tendon-associated genes in vivo. (A) A schematic illustrating the mouse treadmill experiment and the specific treadmill protocol (right). A control mouse was allowed to move freely within the cage. (B) Tendon-associated gene expression following treadmill exercise. Mkx, Tnmd, Col1a1, Col1a2, and Fmod were significantly elevated following treadmill exercise. Treadmill exercise in Mkx−/− mice results in either no change or only a marginal increase in tendon-associated genes. Lipoprotein lipase (Lpl) was selected as a non-tendon-associated gene. Error bars represent standard errors of the means (n = 3) (*, P < 0.05; **, P < 0.01; ***, P < 0.001, two-tailed Student's t test). N.A., not applicable in Mkx−/− mice.
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Figure 1: Mechanical loading induces Mkx and tendon-associated genes in vivo. (A) A schematic illustrating the mouse treadmill experiment and the specific treadmill protocol (right). A control mouse was allowed to move freely within the cage. (B) Tendon-associated gene expression following treadmill exercise. Mkx, Tnmd, Col1a1, Col1a2, and Fmod were significantly elevated following treadmill exercise. Treadmill exercise in Mkx−/− mice results in either no change or only a marginal increase in tendon-associated genes. Lipoprotein lipase (Lpl) was selected as a non-tendon-associated gene. Error bars represent standard errors of the means (n = 3) (*, P < 0.05; **, P < 0.01; ***, P < 0.001, two-tailed Student's t test). N.A., not applicable in Mkx−/− mice.

Mentions: C57BL6/N mice, 10 to 12 weeks old, were placed on a treadmill system (Osaka Microsystem) and were exercised according to their allocated treadmill protocol. Moderate exercise included 12 m/min at 0° inclination for 30 min, 5 days per week, for 4 weeks' duration following a period of acclimatization (Fig. 1A). Three or more mice were used for each RNA analysis. All mice were able to complete their allocated protocol.


Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon.

Kayama T, Mori M, Ito Y, Matsushima T, Nakamichi R, Suzuki H, Ichinose S, Saito M, Marumo K, Asahara H - Mol. Cell. Biol. (2016)

Mechanical loading induces Mkx and tendon-associated genes in vivo. (A) A schematic illustrating the mouse treadmill experiment and the specific treadmill protocol (right). A control mouse was allowed to move freely within the cage. (B) Tendon-associated gene expression following treadmill exercise. Mkx, Tnmd, Col1a1, Col1a2, and Fmod were significantly elevated following treadmill exercise. Treadmill exercise in Mkx−/− mice results in either no change or only a marginal increase in tendon-associated genes. Lipoprotein lipase (Lpl) was selected as a non-tendon-associated gene. Error bars represent standard errors of the means (n = 3) (*, P < 0.05; **, P < 0.01; ***, P < 0.001, two-tailed Student's t test). N.A., not applicable in Mkx−/− mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836271&req=5

Figure 1: Mechanical loading induces Mkx and tendon-associated genes in vivo. (A) A schematic illustrating the mouse treadmill experiment and the specific treadmill protocol (right). A control mouse was allowed to move freely within the cage. (B) Tendon-associated gene expression following treadmill exercise. Mkx, Tnmd, Col1a1, Col1a2, and Fmod were significantly elevated following treadmill exercise. Treadmill exercise in Mkx−/− mice results in either no change or only a marginal increase in tendon-associated genes. Lipoprotein lipase (Lpl) was selected as a non-tendon-associated gene. Error bars represent standard errors of the means (n = 3) (*, P < 0.05; **, P < 0.01; ***, P < 0.001, two-tailed Student's t test). N.A., not applicable in Mkx−/− mice.
Mentions: C57BL6/N mice, 10 to 12 weeks old, were placed on a treadmill system (Osaka Microsystem) and were exercised according to their allocated treadmill protocol. Moderate exercise included 12 m/min at 0° inclination for 30 min, 5 days per week, for 4 weeks' duration following a period of acclimatization (Fig. 1A). Three or more mice were used for each RNA analysis. All mice were able to complete their allocated protocol.

Bottom Line: In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover.Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation.Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems BioMedicine, Tokyo Medical and Dental University, Tokyo, Japan Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan.

No MeSH data available.