Disruption of hedgehog signaling leads to hyoid bone dysplasia during embryogenesis.

The development of the hyoid bone is a complex process that involves the coordination of multiple signaling pathways. Previous studies have demonstrated that disruption of the hedgehog pathway in mice results in a series of structural malformations. However, the specific role and critical period of the hedgehog pathway in the early development of the hyoid bone have not been thoroughly characterized. In this study, we treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage in order to establish a model of hyoid bone dysplasia. Our results indicate that administration of vismodegib at embryonic days 11.5 (E11.5) and E12.5 resulted in the development of hyoid bone dysplasia. We were able to define the critical periods for the induction of hyoid bone deformity through the use of a meticulous temporal resolution. Our findings suggest that the hedgehog pathway plays a crucial role in the early development of the hyoid bone. Additionally, our research has established a novel and easily established mouse model of synostosis in the hyoid bone using a commercially available pathway-selective inhibitor.

Giant cell tumor of hyoid bone: Diagnostic dilemma with a novel management.

Giant cell tumor of bone (GCTB) is locally aggressive tumor occurring in the epiphysis of long bones. GCTBs are uncommon tumors in the head-and-neck region and rarely involve hyoid bone. We report a case of GCTB of hyoid bone. The patient presented with swelling in left submandibular region. The tumor was surgically excised after initial denosumab therapy. Despite adequate resection and rehabilitation, he was tube dependent. Subsequently it was found that the patient had a coexisting myotonic dystrophy, unknown to exist with GCTB of hyoid. Eventually, the patient succumbed to respiratory failure secondary to myotonic dystrophy. GCTB hyoid is a rare presentation posing a diagnostic dilemma. Ours is the first case to report the use of denosumab for GCT in head-and-neck region. Myotonic dystrophy Type I and GCTB are both known to result from abnormality of closely situated foci on chromosome 19.

Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development.

Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1.

Bizarre parosteal osteochondromatous proliferation in the lingual area of the mandibular body versus osteochondroma at the mandibular condyle.

BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is benign and usually occurs in the small tubular bones of the hands and feet, but it is extremely rare in the oral and maxillofacial region. METHODS: The present study compares a case of BPOP occurring in the lingual area of the right mandibular body with a representative case of osteochondroma occurring in the left mandibular condyle using immunohistochemical methods. RESULTS: BPOP showed no continuity to the cortical bone of the mandible on X-ray and was histologically composed of immature cartilage and bone tissues, whereas osteochondroma showed overgrowth of hypertrophic chondrocytes accompanied by mature bone with endochondral ossification. Although BPOP showed no features of cellular atypia or malignant transformation, it expressed more osteogenic proteins, including BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF, than osteochondroma. Furthermore, the perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP showed stronger immunoreaction of PCNA, p53, ß-catenin, BCL2, pAKT, survivin, 14-3-3, CEA, EMA, pan-K, and S-100 than the tumor cells of osteochondroma. CONCLUSIONS: Therefore, it was presumed that similar to embryonal osteochondroid tissue, BPOP might be activated by osteogenic and oncogenic signaling and that this increased signaling may explain the rapid growth and high recurrence of BPOP.

Rostral and caudal pharyngeal arches share a common neural crest ground pattern.

In vertebrates, face and throat structures, such as jaw, hyoid and thyroid cartilages develop from a rostrocaudal metameric series of pharyngeal arches, colonized by cranial neural crest cells (NCCs). Colinear Hox gene expression patterns underlie arch specific morphologies, with the exception of the first (mandibular) arch, which is devoid of any Hox gene activity. We have previously shown that the first and second (hyoid) arches share a common, Hox-free, patterning program. However, whether or not more posterior pharyngeal arch neural crest derivatives are also patterned on the top of the same ground-state remained an unanswered question. Here, we show that the simultaneous inactivation of all Hoxa cluster genes in NCCs leads to multiple jaw and first arch-like structures, partially replacing second, third and fourth arch derivatives, suggesting that rostral and caudal arches share the same mandibular arch-like ground patterning program. The additional inactivation of the Hoxd cluster did not significantly enhance such a homeotic phenotype, thus indicating a preponderant role of Hoxa genes in patterning skeletogenic NCCs. Moreover, we found that Hoxa2 and Hoxa3 act synergistically to pattern third and fourth arch derivatives. These results provide insights into how facial and throat structures are assembled during development, and have implications for the evolution of the pharyngeal region of the vertebrate head.

Distribution of tenascin-C and -X, and soft X-ray analysis of the mandibular symphysis during mandible formation in the human fetus.

In the development of the human mandible, the process of bone calcification, distribution and expression of tenascin-C and -X in the mental symphyseal region are unknown. The purpose of this study was to determine the distribution of these extracellular matrices in the connective tissue around calcified tissues located on the mental symphyseal region of the human fetus during development through histological and radiographical studies. The radiographic density increased from 16 weeks to 24 weeks gestation in all examined regions; in contrast, the diameter of muscle fiber in the suprahyoid muscles (digastric anterior and geniohyoid muscles) inserted into the inner mental symphyseal region increased from 24 weeks gestation. The extracellular matrices (tenascin) were shown to have a different distribution in the mental symphyseal region of the human fetus at each stage. These different distributions of tenascin-C and -X were found around the epithelium and the endomysium of the mental symphyseal region, and affect the specific formation of the mandible during ossification with hyoid muscle development in human fetus.

Mineralization of stylohyoid ligament complex in patients with temporomandibular disorders and asymptomatic individuals: a comparative study.

The incidence of mineralization of the stylohyoid ligament complex, according to radiographic findings, was analysed in a group of patients with temporomandibular disorders (TMD), and compared with that of a control group of asymptomatic individuals (AI). Both groups were similar considering the prevalence of the female gender as well as the distribution of cases according to age. 'Elongated' was the most frequent radiographic appearance in both groups; 'partially mineralized' was the most frequent radiographic pattern in the TMD group; and the lower ramus was the most frequent location of mineralization in both groups. When comparing between groups and according to each class, there was only one significant difference in radiographic appearance, 'pseudoarticulated' being more frequent in the TMD group. We can conclude that the occurrence and characteristics of mineralization of stylohyoid ligament complex were similar in TMD patients and AIs.