Significance of the Tks4 scaffold protein in bone tissue homeostasis

Virag Vas, T. Kovács, Szandra Körmendi, Andrea Bródy, Gyöngyi Kudlik, Bálint Szeder, Diána Mező, Dóra Kállai, Kitti Koprivanacz, Balázs L. Merő, Metta Dülk, J. Tóvári, Péter Vajdovich, Neslihan Şenel, Ilknur Özcan, Z. Helyes, Csaba Dobó-Nagy, L. Buday

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5781
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Mesenchymal Stromal Cells
Homeostasis
Bone and Bones
Knockout Mice
Osteoporosis
Proteins
Osteoblasts
Osteogenesis
Femur
Facial Bones
Inborn Genetic Diseases
Porosity
Osteocalcin
Bone Resorption
Thigh
Skull
Ear
Bone Marrow
Phenotype
Ter Haar syndrome

ASJC Scopus subject areas

  • General

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Significance of the Tks4 scaffold protein in bone tissue homeostasis. / Vas, Virag; Kovács, T.; Körmendi, Szandra; Bródy, Andrea; Kudlik, Gyöngyi; Szeder, Bálint; Mező, Diána; Kállai, Dóra; Koprivanacz, Kitti; Merő, Balázs L.; Dülk, Metta; Tóvári, J.; Vajdovich, Péter; Şenel, Neslihan; Özcan, Ilknur; Helyes, Z.; Dobó-Nagy, Csaba; Buday, L.

In: Scientific reports, Vol. 9, No. 1, 5781, 01.12.2019.

Research output: Contribution to journalArticle

Vas, V, Kovács, T, Körmendi, S, Bródy, A, Kudlik, G, Szeder, B, Mező, D, Kállai, D, Koprivanacz, K, Merő, BL, Dülk, M, Tóvári, J, Vajdovich, P, Şenel, N, Özcan, I, Helyes, Z, Dobó-Nagy, C & Buday, L 2019, 'Significance of the Tks4 scaffold protein in bone tissue homeostasis', Scientific reports, vol. 9, no. 1, 5781. https://doi.org/10.1038/s41598-019-42250-6
Vas, Virag ; Kovács, T. ; Körmendi, Szandra ; Bródy, Andrea ; Kudlik, Gyöngyi ; Szeder, Bálint ; Mező, Diána ; Kállai, Dóra ; Koprivanacz, Kitti ; Merő, Balázs L. ; Dülk, Metta ; Tóvári, J. ; Vajdovich, Péter ; Şenel, Neslihan ; Özcan, Ilknur ; Helyes, Z. ; Dobó-Nagy, Csaba ; Buday, L. / Significance of the Tks4 scaffold protein in bone tissue homeostasis. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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AU - Kudlik, Gyöngyi

AU - Szeder, Bálint

AU - Mező, Diána

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AU - Koprivanacz, Kitti

AU - Merő, Balázs L.

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AU - Tóvári, J.

AU - Vajdovich, Péter

AU - Şenel, Neslihan

AU - Özcan, Ilknur

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