Nuclear Localization and Chromatin Association of Tenomodulin in Human and Equine Tenocytes

Qi J, Banes AN, Dmochowski JM, Norman W, Kim J, Bynum D, Patterson M, Creighton A, Banes AJ. 14th Annual Conference of the North Carolina Tissue Engineering and Regenerative Medicine Society, Raleigh, NC, September 10, 2012.

Tenomodulin (Tnmd) is classified as a type II transmembrane glycoprotein with a BRICHOS domain, and is highly expressed in developing as well as in mature tendons. Tnmd has been reported to have anti-angiogenic properties but results in a knockout mouse model did not substantiate that claim. We have reported that Tnmd translocated into the nucleus in response to stretch and knockdown of Tnmd with RNAi, reduced cell proliferation. However, the function of Tnmd in the nucleus is still unknown. We also reported that stretch induced the expression of interleukin-1beta (IL-1beta) in tenocytes. Therefore, we hypothesized that IL-1beta might induce nuclear localization of Tnmd and that Tnmd might associate with chromatin during mitosis. Since IL-1beta is key player in tedinopathy, this study may shine a light on the treatment of tendinopathy in the future. In the present study, Tnmd showed nuclear localization at less than 8 h in response to cyclic stretching. Treatment of tenocytes with IL-1beta also induced Tnmd nuclear localization within 8 h. Tnmd showed nuclear localization in almost all of the cells at 8 h post-addition of IL-1beta. Surprisingly, immunochemically detectable Tnmd co-localized with chromatin during mitosis from prometaphase to telophase in human and equine tenocytes at 8 h post-addition of IL-1beta. Given a role in cell proliferation and a nuclear localization, we speculate that Tnmd plays a role in cell cycle regulation. Since IL-1beta is a key player in tendinopathy, this study may lead to a better treatment for tendinopathy.