RESUMEN
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.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anomalías Craneofaciales/genética , Cardiopatías Congénitas/genética , Homeostasis , Osteocondrodisplasias/congénito , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Médula Ósea/metabolismo , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/metabolismo , Hueso Esponjoso/patología , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Anomalías Craneofaciales/metabolismo , Anomalías Craneofaciales/patología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/metabolismo , Discapacidades del Desarrollo/patología , Fémur/diagnóstico por imagen , Fémur/metabolismo , Fémur/patología , Cardiopatías Congénitas/metabolismo , Cardiopatías Congénitas/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Osteocalcina/genética , Osteocalcina/metabolismo , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patología , Osteogénesis , Adulto JovenRESUMEN
Frank-ter Haar syndrome is a genetic disease that is transmitted by autosomal recessive pattern with characteristic features such as megalocornea or glaucoma, a prominent coccyx, heart defects, developmental delays, brachycephaly, a wide anterior fontanel, finger flexion deformities, full cheeks and micrognathia. Dentomaxillofacial features of this syndrome are not well documented in the literature. We present of a 21-year-old male with Frank-ter Haar syndrome and some features that may be linked with this syndrome not reported before in the literature.