Vas, Virág and Kovács, Tamás and Körmendi, Szandra Katalin and Bródy, Andrea and Kudlik, Gyöngyi and Szeder, Bálint and Koprivanacz, Kitti and Merő, Balázs László and Dülk, Metta and Tóvári, József and Helyes, Zsuzsanna and Dobó Nagy, Csaba and Buday, László (2019) Significance of the Tks4 scaffold protein in bone tissue homeostasis. SCIENTIFIC REPORTS, 9 (1). ISSN 2045-2322
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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.
| Item Type: | Article |
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| Additional Information: | Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary Department of Prosthodontics, Faculty of Dentistry, Semmelweis University, Budapest, Hungary Department of Oral Diagnostics, Faculty of Dentistry, Semmelweis University, Budapest, Hungary Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary Department and Clinic of Internal Medicine, Szent Istvan University, Faculty of Veterinary Science, Budapest, Hungary Oral and Maxillofacial Radiology Department, Faculty of Dentistry at Istanbul University, Istanbul, Turkey University of Pécs, Medical School, Department of Pharmacology and Pharmacotherapy, János Szentágothai Research Centre, Molecular Pharmacology Research Team & Centre for Neuroscience, Pécs, Hungary Department of Medical Chemistry, Semmelweis University Medical School, Budapest, Hungary Export Date: 8 May 2019 Correspondence Address: Vas, V.; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: vas.virag@ttk.mta.hu |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 04 Aug 2019 09:16 |
| Last Modified: | 04 Aug 2019 09:16 |
| URI: | http://real.mtak.hu/id/eprint/95056 |
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