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bioRxiv · 10.1101/2023.11.13.566892

The LINC complex regulates Achilles tendon elastic modulus, Achilles and tail tendon collagen crimp, and Achilles and tail tendon lateral expansion during early postnatal development.

Pancheri, N. M.·Daw, J. T.·Ditton, D.·Schiele, N. R.·Birks, S.·Uzer, G.·Jones, C. L.·Penney, B. T.·Theodossiou, S. K.
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Abstract

There is limited understanding of how mechanical signals regulate tendon development. The nucleus has emerged as a major regulator of cellular mechanosensation, via the linker of nucleoskeleton and cytoskeleton (LINC) protein complex. Specific roles of LINC in tenogenesis have not been explored. In this study, we investigate how LINC regulates tendon development by disabling LINC-mediated mechanosensing via dominant negative (dn) expression of the Klarsicht, ANC-1, and Syne Homology (KASH) domain, which is necessary for LINC to function. We hypothesized that LINC regulates mechanotransduction in developing tendon, and that disabling LINC would impact tendon mechanical properties and structure in a mouse model of dnKASH. We used Achilles (AT) and tail (TT) tendons as representative energy-storing and limb-positioning tendons, respectively. Mechanical testing at postnatal day 10 showed that disabling the LINC complex via dnKASH significantly impacted tendon mechanical properties and cross-sectional area, and that effects differed between ATs and TTs. Collagen crimp distance was also impacted in dnKASH tendons, and was significantly decreased in ATs, and increased in TTs. Overall, we show that disruption to the LINC complex specifically impacts tendon mechanics and collagen crimp structure, with unique responses between an energy-storing and limb-positioning tendon. This suggests that nuclear mechanotransduction through LINC plays a role in regulating tendon formation during neonatal development.

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Pancheri, N. M., Daw, J. T., Ditton, D., Schiele, N. R., Birks, S., Uzer, G., Jones, C. L., Penney, B. T., Theodossiou, S. K.. 2023-11-13. The LINC complex regulates Achilles tendon elastic modulus, Achilles and tail tendon collagen crimp, and Achilles and tail tendon lateral expansion during early postnatal development.. https://doi.org/10.1101/2023.11.13.566892

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