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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.


Related in: MedlinePlus

Mkx-deficient tendon fibers fail to respond to mechanical loads. (A) Transmission electron microscopy (TEM) of mouse Achilles tendon. WT and Mkx−/− collagen fibers from mice with or without exercise are shown. Magnification, ×50,000; scale bar, 500 nm. (B) The collagen fiber diameter distribution graph shows an increase in the distribution of WT mouse fibers but no change was observed in Mkx−/− mice. (C) Mean collagen fiber diameter demonstrated an increase in collagen fiber diameter with treadmill exercise for WT mice but not in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (***, P < 0.001, two-tailed Student's t test). (D) Achilles tendon fiber numbers were calculated per area, revealing increased fiber density in the treadmill group for WT mice which was, again, not observed in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (*, P < 0.05, two-tailed Student's t test).
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Figure 2: Mkx-deficient tendon fibers fail to respond to mechanical loads. (A) Transmission electron microscopy (TEM) of mouse Achilles tendon. WT and Mkx−/− collagen fibers from mice with or without exercise are shown. Magnification, ×50,000; scale bar, 500 nm. (B) The collagen fiber diameter distribution graph shows an increase in the distribution of WT mouse fibers but no change was observed in Mkx−/− mice. (C) Mean collagen fiber diameter demonstrated an increase in collagen fiber diameter with treadmill exercise for WT mice but not in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (***, P < 0.001, two-tailed Student's t test). (D) Achilles tendon fiber numbers were calculated per area, revealing increased fiber density in the treadmill group for WT mice which was, again, not observed in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (*, P < 0.05, two-tailed Student's t test).

Mentions: In order to assess whether the altered gene expression of Col1a1, Col1a2, and Fmod, the components of tendon ECM, is reflected at the tissue level, transmission electron microscopy (TEM) was performed in WT and Mkx−/− mice with and without treadmill exercise. Transverse Achilles tendon sections revealed an increase in collagen fiber diameter after treadmill exercise in WT mice (Fig. 2A and B) (28). However, in the Mkx−/− mouse, not only did the Achilles tendons display reduced collagen diameters, but collagen fiber in the absence of Mkx also failed to increase in size in response to physical exercise (Fig. 2C). This suggests that Mkx is involved not only in tendon development but also in the tendon response system to physical stimulation that is necessary for the formation of proper tendon fibers.


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)

Mkx-deficient tendon fibers fail to respond to mechanical loads. (A) Transmission electron microscopy (TEM) of mouse Achilles tendon. WT and Mkx−/− collagen fibers from mice with or without exercise are shown. Magnification, ×50,000; scale bar, 500 nm. (B) The collagen fiber diameter distribution graph shows an increase in the distribution of WT mouse fibers but no change was observed in Mkx−/− mice. (C) Mean collagen fiber diameter demonstrated an increase in collagen fiber diameter with treadmill exercise for WT mice but not in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (***, P < 0.001, two-tailed Student's t test). (D) Achilles tendon fiber numbers were calculated per area, revealing increased fiber density in the treadmill group for WT mice which was, again, not observed in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (*, P < 0.05, two-tailed Student's t test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Mkx-deficient tendon fibers fail to respond to mechanical loads. (A) Transmission electron microscopy (TEM) of mouse Achilles tendon. WT and Mkx−/− collagen fibers from mice with or without exercise are shown. Magnification, ×50,000; scale bar, 500 nm. (B) The collagen fiber diameter distribution graph shows an increase in the distribution of WT mouse fibers but no change was observed in Mkx−/− mice. (C) Mean collagen fiber diameter demonstrated an increase in collagen fiber diameter with treadmill exercise for WT mice but not in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (***, P < 0.001, two-tailed Student's t test). (D) Achilles tendon fiber numbers were calculated per area, revealing increased fiber density in the treadmill group for WT mice which was, again, not observed in Mkx−/− mice. Data were calculated from three different views (each, n = 100). Error bars represent standard errors of the means (*, P < 0.05, two-tailed Student's t test).
Mentions: In order to assess whether the altered gene expression of Col1a1, Col1a2, and Fmod, the components of tendon ECM, is reflected at the tissue level, transmission electron microscopy (TEM) was performed in WT and Mkx−/− mice with and without treadmill exercise. Transverse Achilles tendon sections revealed an increase in collagen fiber diameter after treadmill exercise in WT mice (Fig. 2A and B) (28). However, in the Mkx−/− mouse, not only did the Achilles tendons display reduced collagen diameters, but collagen fiber in the absence of Mkx also failed to increase in size in response to physical exercise (Fig. 2C). This suggests that Mkx is involved not only in tendon development but also in the tendon response system to physical stimulation that is necessary for the formation of proper tendon fibers.

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.


Related in: MedlinePlus