Cranial Base Synchondrosis Lacks PTHrP-Expressing Column-Forming Chondrocytes.

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as the growth center of the skull. The synchondrosis is composed of bidirectional opposite-facing layers of resting, proliferating, and hypertrophic chondrocytes, and lacks the secondary ossification center. In long bones, the resting zone of the epiphyseal growth plate houses a population of parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to the formation of columnar chondrocytes. Whether PTHrP+ chondrocytes in the synchondrosis possess similar functions remains undefined. Using Pthrp-mCherry knock-in mice, we found that PTHrP+ chondrocytes predominantly occupied the lateral wedge-shaped area of the synchondrosis, unlike those in the femoral growth plate that reside in the resting zone within the epiphysis. In vivo cell-lineage analyses using a tamoxifen-inducible Pthrp-creER line revealed that PTHrP+ chondrocytes failed to establish columnar chondrocytes in the synchondrosis. Therefore, PTHrP+ chondrocytes in the synchondrosis do not possess column-forming capabilities, unlike those in the resting zone of the long bone growth plate. These findings support the importance of the secondary ossification center within the long bone epiphysis in establishing the stem cell niche for PTHrP+ chondrocytes, the absence of which may explain the lack of column-forming capabilities of PTHrP+ chondrocytes in the cranial base synchondrosis.

Oral Lichen Planus-Associated Oral Cavity Squamous Cell Carcinoma Is Associated With Improved Survival and Increased Risk of Recurrence.

PURPOSE: We investigated the overall survival (OS), disease-specific survival (DSS), and disease-free survival among patients with oral lichen planus-associated oral cavity squamous cell carcinoma (OLP-OCSCC). The secondary objective was to assess the annual risk of tumor recurrence or second primary tumor (SPT). MATERIALS AND METHODS: A comparative retrospective study was performed of patients with OLP-OCSCC presenting between June 2007 and December 2018 to the Department of Oral and Maxillofacial Surgery, Michigan Medicine (Ann Arbor, MI) and patients with OCSCC in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2015). RESULTS: A total of 87 patients with OLP-OCSCC met the inclusion criteria, and 55,165 patients with OCSCC from the SEER database were included. The proportion of women was greater in the OLP group than in the SEER group (56.3 vs 38.0%; P < .001). In the OLP group, 47.1% had no smoking history and 43.7% had no alcohol history. Most patients in the OLP group had presented with stage I disease (46.0%) compared with 31.7% in the SEER group (P = .004). Overall, the OS and DSS were significantly greater in the OLP group than in the SEER group at all points from 1 to 5 years (P ≤ .01). In the OLP group, 46 patients (52.9%) had at least 1 recurrence or SPT. At 10 years, the predicted mean number of recurrences was 1.93 per patient (95% confidence interval, 1.56 to 2.39). CONCLUSIONS: OLP-OCSCC frequently affects women, nonsmokers, and nondrinkers and presents with localized disease at a high frequency. Patients with OLP-OCSCC have increased OS and DSS and a greater risk of tumor recurrence or SPT compared with OCSCC in the general population. Lifelong, frequent surveillance is recommended for patients with OLP-OCSCC owing to the risk of late recurrence. Future studies are needed to understand the pathophysiology of OLP-OCSCC.

Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds.

WNT10A is a signaling molecule involved in tooth development, and WNT10A defects are associated with tooth agenesis. We characterized Wnt10a null mice generated by the knockout mouse project (KOMP) and six families with WNT10A mutations, including a novel p.Arg104Cys defect, in the absence of EDA,EDAR, or EDARADD variations. Wnt10a null mice exhibited supernumerary mandibular fourth molars, and smaller molars with abnormal cusp patterning and root taurodontism. Wnt10a (-/-) incisors showed distinctive apical-lingual wedge-shaped defects. These findings spurred us to closely examine the dental phenotypes of our WNT10A families. WNT10A heterozygotes exhibited molar root taurodontism and mild tooth agenesis (with incomplete penetrance) in their permanent dentitions. Individuals with two defective WNT10A alleles showed severe tooth agenesis and had fewer cusps on their molars. The misshapened molar crowns and roots were consistent with the Wnt10a null phenotype and were not previously associated with WNT10A defects. The missing teeth contrasted with the presence of supplemental teeth in the Wnt10a null mice and demonstrated mammalian species differences in the roles of Wnt signaling in early tooth development. We conclude that molar crown and root dysmorphologies are caused by WNT10A defects and that the severity of the tooth agenesis correlates with the number of defective WNT10A alleles.

Hypomaturation amelogenesis imperfecta caused by a novel SLC24A4 mutation.

In this case report of autosomal recessive pigmented hypomaturation amelogenesis imperfecta (AI), we identify a novel homozygous missense mutation (g.165151 T>G; c.1317 T>G; p.Leu436 Arg) in SLC24A4, a gene encoding a potassium-dependent sodium-calcium exchanger that is critical for hardening dental enamel during tooth development.