Significance of the Tks4 scaffold protein in bone tissue homeostasis

Abstract The main driver of osteoporosis is an imbalance between bone resorption and formation. The pathogenesis of osteoporosis has also been connected to genetic alterations in key osteogenic factors and dysfunction of bone marrow mesenchymal stem/stromal cells (BM-MSCs). Tks4 (encoded by the Sh3p...

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Autores principales:	Virag Vas, Tamás Kovács, Szandra Körmendi, Andrea Bródy, Gyöngyi Kudlik, Bálint Szeder, Diána Mező, Dóra Kállai, Kitti Koprivanacz, Balázs L. Merő, Metta Dülk, József Tóvári, Péter Vajdovich, Ş. Neslihan Şenel, Ilknur Özcan, Zsuzsanna Helyes, Csaba Dobó-Nagy, László Buday
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96550bcba65a4bb08c3d5a75f608f18c
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spelling	oai:doaj.org-article:96550bcba65a4bb08c3d5a75f608f18c2021-12-02T15:08:07ZSignificance of the Tks4 scaffold protein in bone tissue homeostasis10.1038/s41598-019-42250-62045-2322https://doaj.org/article/96550bcba65a4bb08c3d5a75f608f18c2019-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-42250-6https://doaj.org/toc/2045-2322Abstract The main driver of osteoporosis is an imbalance between bone resorption and formation. The pathogenesis of osteoporosis has also been connected to genetic alterations in key osteogenic factors and dysfunction of bone marrow mesenchymal stem/stromal cells (BM-MSCs). Tks4 (encoded by the Sh3pxd2b gene) is a scaffold protein involved in podosome organization. Homozygous mutational inactivation of Sh3pxd2b causes Frank-ter Haar syndrome (FTHS), a genetic disease that affects bone tissue as well as eye, ear, and heart functions. To date, the role of Tks4 in adult bone homeostasis has not been investigated. Therefore, the aim of this study was to analyze the facial and femoral bone phenotypes of Sh3pxd2b knock-out (KO) mice using micro-CT methods. In addition to the analysis of the Sh3pxd2b-KO mice, the bone microstructure of an FTHS patient was also examined. Macro-examination of skulls from Tks4-deficient mice revealed craniofacial malformations that were very similar to symptoms of the FTHS patient. The femurs of the Sh3pxd2b-KO mice had alterations in the trabecular system and showed signs of osteoporosis, and, similarly, the FTHS patient also showed increased trabecular separation/porosity. The expression levels of the Runx2 and osteocalcin bone formation markers were reduced in the bone and bone marrow of the Sh3pxd2b-KO femurs, respectively. Our recent study demonstrated that Sh3pxd2b-KO BM-MSCs have a reduced ability to differentiate into osteoblast lineage cells; therefore, we concluded that the Tks4 scaffold protein is important for osteoblast formation, and that it likely plays a role in bone cell homeostasis.Virag VasTamás KovácsSzandra KörmendiAndrea BródyGyöngyi KudlikBálint SzederDiána MezőDóra KállaiKitti KoprivanaczBalázs L. MerőMetta DülkJózsef TóváriPéter VajdovichŞ. Neslihan ŞenelIlknur ÖzcanZsuzsanna HelyesCsaba Dobó-NagyLászló BudayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Virag Vas Tamás Kovács Szandra Körmendi Andrea Bródy Gyöngyi Kudlik Bálint Szeder Diána Mező Dóra Kállai Kitti Koprivanacz Balázs L. Merő Metta Dülk József Tóvári Péter Vajdovich Ş. Neslihan Şenel Ilknur Özcan Zsuzsanna Helyes Csaba Dobó-Nagy László Buday Significance of the Tks4 scaffold protein in bone tissue homeostasis
description	Abstract The main driver of osteoporosis is an imbalance between bone resorption and formation. The pathogenesis of osteoporosis has also been connected to genetic alterations in key osteogenic factors and dysfunction of bone marrow mesenchymal stem/stromal cells (BM-MSCs). Tks4 (encoded by the Sh3pxd2b gene) is a scaffold protein involved in podosome organization. Homozygous mutational inactivation of Sh3pxd2b causes Frank-ter Haar syndrome (FTHS), a genetic disease that affects bone tissue as well as eye, ear, and heart functions. To date, the role of Tks4 in adult bone homeostasis has not been investigated. Therefore, the aim of this study was to analyze the facial and femoral bone phenotypes of Sh3pxd2b knock-out (KO) mice using micro-CT methods. In addition to the analysis of the Sh3pxd2b-KO mice, the bone microstructure of an FTHS patient was also examined. Macro-examination of skulls from Tks4-deficient mice revealed craniofacial malformations that were very similar to symptoms of the FTHS patient. The femurs of the Sh3pxd2b-KO mice had alterations in the trabecular system and showed signs of osteoporosis, and, similarly, the FTHS patient also showed increased trabecular separation/porosity. The expression levels of the Runx2 and osteocalcin bone formation markers were reduced in the bone and bone marrow of the Sh3pxd2b-KO femurs, respectively. Our recent study demonstrated that Sh3pxd2b-KO BM-MSCs have a reduced ability to differentiate into osteoblast lineage cells; therefore, we concluded that the Tks4 scaffold protein is important for osteoblast formation, and that it likely plays a role in bone cell homeostasis.
format	article
author	Virag Vas Tamás Kovács Szandra Körmendi Andrea Bródy Gyöngyi Kudlik Bálint Szeder Diána Mező Dóra Kállai Kitti Koprivanacz Balázs L. Merő Metta Dülk József Tóvári Péter Vajdovich Ş. Neslihan Şenel Ilknur Özcan Zsuzsanna Helyes Csaba Dobó-Nagy László Buday
author_facet	Virag Vas Tamás Kovács Szandra Körmendi Andrea Bródy Gyöngyi Kudlik Bálint Szeder Diána Mező Dóra Kállai Kitti Koprivanacz Balázs L. Merő Metta Dülk József Tóvári Péter Vajdovich Ş. Neslihan Şenel Ilknur Özcan Zsuzsanna Helyes Csaba Dobó-Nagy László Buday
author_sort	Virag Vas
title	Significance of the Tks4 scaffold protein in bone tissue homeostasis
title_short	Significance of the Tks4 scaffold protein in bone tissue homeostasis
title_full	Significance of the Tks4 scaffold protein in bone tissue homeostasis
title_fullStr	Significance of the Tks4 scaffold protein in bone tissue homeostasis
title_full_unstemmed	Significance of the Tks4 scaffold protein in bone tissue homeostasis
title_sort	significance of the tks4 scaffold protein in bone tissue homeostasis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/96550bcba65a4bb08c3d5a75f608f18c
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Significance of the Tks4 scaffold protein in bone tissue homeostasis

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