Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Oral and craniofacial findings in a patient with methylmalonic aciduria and homocystinuria: review and a case report.

Combined methylmalonic aciduria and homocystinuria (MMA-HC) is a rare metabolic disease characterized by an inborn defect in B12 vitamin metabolism. This case report concerns an 11-year-old patient with MMA-HC, which developed during the neonatal period. The patient shows some of the facial features that were already reported in the literature (high forehead, large floppy, low-set ears, flat philtrum and hypotonia of perioral and masticatory muscles) but no dolichocephalic skull nor long face. The patient also shows signs that had not been previously described: epicanthal folds, broad nasal bridge, long and flat philtrum, amimic expression and, particularly, a postural alteration (the head is rotated and bent towards the left shoulder, which is lower than the right one). Such alteration can be attributed to visual impairment and is responsible for breaking muscular and skeletal balance in the frontal plane, thus causing the horizontal planes of both maxillary bones to converge towards the right--as highlighted by the cephalometric analysis of the Teleradio-graph of the skull in Posteroanterior projection according to Ricketts. As for the patient's teeth, eruption times are normal, but there are anomalies of shape (chisel-like central incisors). As far as dental caries is concerned, the patient's DMFT is 4 (D=4, M=0, F=0). This clinical case highlights the need for dental prevention programs suggested by the pediatrician once the pathology is diagnosed

Craniofacial changes and treatment of the stomatognathic system in subjects with Cleidocranial dysplasia

AIM: Cleidocranial dysplasia (CCD) is a rare disorder that is inherited as an autosomal genetic trait. It is characterised by defective ossification, delayed bone and tooth development, stomatognathic and craniofacial abnormalities and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. CCD is a dental disease that needs complex rehabilitation and the assistance of several specialists. In most cases, this disease precipitates towards the end of childhood with the progressive morbidity of the deciduous dentition, thus leading to edentulism at a young age and giving patients an older appearance. Several therapeutic approaches have been proposed within literature. The aim of this paper is to revise the literature on the proposed therapeutic approaches for the functional and aesthetical rehabilitation of the typical defects caused by CCD in the cephalic region, and to identify the most effective therapy currently available. CONCLUSIONS: The most effective therapeutic approach for the early treatment of the orthodontic and orthopaedic diseases in CCD patients would start with an orthopaedic treatment of the upper jaw followed by orthodontic and surgical treatments. When growth is completed a reintervention for maxillofacial surgery and the orthodontic treatment may be required. Finally, if some teeth are missing. function and aesthetics can be achieved replacing them with prosthesis

Cleidocranial dysplasia: etiology and stomatognathic and craniofacial abnormalities

Cleidocranial dysplasia (CCD) is a rare disorder which is inherited as an autosomal genetic trait. It is characterized by defective ossification, delayed bone and tooth development, stomatognathic and craniofacial abnormalities, and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. The purpose of this review is to collect and analyze data in the literature on orofacial typical manifestations of the syndrome and to present knowledge of the eziopatogenics mechanisms of the CCD. Clinical, genetic, aetiopathogenetic studies on this syndrome were compliled through a systematic approach using Medline. This review reports the cranio-facial features and dental characteristics of the CCD on the basis of all data in the literature. This review pays particular attention on the eziopatogenics mechanisms of CCD and summarises the results of the most recent studies. Access to detailed review of the etiopathogenic mechanisms of CCD is a fundamental support for clinicians as it can allow to make an informed assessment regarding the most effective choice of therapy. The review shows how an interdisciplinary approach is necessary for an appropriate treatment since CCD patients suffer from a skeletal third class, transverse deficiency of the maxilla, supernumerary permanent teeth and deficient eruption of impacted permanent teeth

il paziente con deficit di ormone della crescita

Il capitolo rivolge l'attenzione alle patologie del distretto oro-cefalico del paziente pediatrico affetto da deficit di GH, offrendo indicazioni di diagnosi e terapia sulla base dell'esperienza clinica e delle evidenze presenti in letteratura

Caries and adolescents.

The rapid improvement in oral health conditions in childhood and adolescence and the ceaseless bombardment of information from the mass media have, during little more than 30 years, brought about a decrease in the prevalence of caries of more than 70% in most European Union countries. The study aimed to take an accurate picture of oral health conditions and dental prevention habits among adolescents. METHODS: The research was conducted on a group of 340 adolescents (12-16 years) in the province of Bologna (Imola) and used the SPSS to compare clinical and epidemiological parameters with medical-history data traditionally understood to be determinant for caries. RESULTS: From an analysis of the data it emerged that the mean value of the decay, missing or filled tooth (DMFT) index in the group was 1.8765 +/- 2.1987 and that the plaque index (according to L\uf6e and Silness) was 1.2519 +/- 0.4213. CONCLUSIONS: Crossing the data obtained, a highly significant correlation emerged (P=0.004) between plaque and caries indexes, and confirmed the primary role of bacterial plaque in causing caries. Unlike what we expected and unlike data reported in the international literature, the caries index was not found to be correlated in a statistically significant way with frequency of brushing, ''preferential consumption of sweet snacks'' (P=0.231) nor ''eating sweets and chewing gum'' (P=0.159) or with taking fluoride tablets (P=0.406). The key to success during adolescence is rooted in childhood; it is the pediatricians' and parents' job to guide and control the acquisition of correct dietary and oral hygiene habits

Sindrome del nevo epidermolitico in et\ue0 pediatrica: aspetti odontostomatologici

UN BAMBINO DI 4 ANNI, AFFETTO DA SINDROME DEL NEVO EPIDERMOLITICO, RITARDO MENTALE E CARDIOPATIA CONGENITA CIANOGENA, SI \uc8 PRESENTATO ALLA NOSTRA ATTENZIONE PER UNA VALUTAZIONE ODONTOSTOMATOLOGICA. L\u2019ESAME OBIETTIVO HA EVIDENZIATO EMIPERTROFIA DESTRA DELLA FACCIA E DELLA LINGUA, FORMULA DENTARIA DECIDUA COMPLETA E NELLA SEDE DELL\u2019EMIPERTROFIA, PRESENZA DELL\u2019ELEMENTO 1.6 E 4.6, IGIENE ORALE INSUFFICIENTE E LESIONI CARIOSE DESTRUENTI CON PRESENZA DI PATOLOGIE PERIAPICALI SUPPURATIVE. I GENITORI HANNO RIFERITO LA NECESSIT\uc0 DI RIPETUTE TERAPIE ANTIBIOTICHE PER ASCESSI RICORRENTI. IN RELAZIONE ALLA NECESSIT\uc0 DI UNA RISOLUZIONE TERAPEUTICA IN TEMPI RIDOTTI, AL FINE DI ELIMINARE E LE INFEZIONI E DI DIMINUIRE IL RISCHIO DI ENDOCARDITE BATTERICA, A CAUSA DELLA MANACNZA DI COLLABORAZIONE, SI \uc8 DECISO DI TRATTARE IL PAZIENTE IN ANESTESIA GENERALE. NELLA SEDUTA OPERATORIA (DICEMBRE 2001) SONO STATE EFFETTUATE LE TERAPIE CONSERVATIVE DEGLI ELEMENTI DECIDUI RECUPERABILI E DEI PERMANENTI, L\u2019ESTRAZIONE DEGLI ELEMENTI DECIDUI AFFETTI DA CARIE DESTRUENTI E IGIENE ORALE PROFESSIONALE. IN SEGUITO IL BAMBINO \uc8 STATO INSERITO IN UN PROGRAMMA DI CONTROLLI IGIENICI BIMESTRALI NEL CORSO DEI QUALI SI \uc8 RISCONTRATO UN GRADUALE E PROGRESSIVO AUMENTO DELLA COLLABORAZIONE. LA TEMPESTIVA RISOLUZIONE DELLA SINTOMATOLOGIA DOLOROSA HA PERMESSO UNA GRADUALIT\uc0 NELL\u2019APPROCCIO CHE HA CONSENTITO DI GUADAGNARE E MANTENERE LA COMPLIANCE ALLA SEDUTA ODONTOIATRICA ANCHE IN UN BAMBINO STRESSATO DALLE NUMEROSE OSPEDALIZZAZIONI E CON RITARDO MENTALE