Dura cells in the etiopathogenesis of Crouzon syndrome: the effects of FGFR2 mutations in the dura cells on the proliferation of osteoblasts through the hippo/YAP mediated transcriptional regulation pathway.

BACKGROUND: FGFR2 (fibroblast growth factor receptor 2) mutations are implicated in the etiopathogenesis of syndromic craniosynostosis, and C278F- or C342Y-FGFR2 mutations can lead to Crouzon syndrome. The dura mater exerts crucial effects in the regulation of cranial suture development. However, the underlying mechanisms of these biological processes are rarely studied. This research explored and analyzed the biological function of FGFR2 overexpressed by dura cells on cranial osteoblasts. METHODS: Dura cells and cranial osteoblasts from C57BL/6 mice aged 6 days were obtained and cultured respectively. Lentivirus-FGFR2 constructs were engineered with C278F- and C342Y-FGFR2 mutations. The dura cells were infected with the constructs and co-cultured with osteoblasts in a trans-well system. Four experimental groups were established, namely the Oste group, the Oste+Dura-vector group, the Oste+Dura-C278F group, and the Oste+Dura-C342Y group. FACS, CCK8, and EdU assays were used to evaluate the osteoblast proliferation levels. Western blot and RT-qPCR were used to measure the expressions of the factors related to proliferation, differentiation, and apoptosis. Furthermore, the expression levels of the key factors in the Hippo/YAP-PI3K-AKT proliferation pathway were measured and analyzed. Finally, rescue experiments were performed with an RNA interfering assay. RESULTS: The proliferation and differentiation levels of the osteoblasts in the Oste+Dura-C278F and Oste+Dura-C342Y groups were significantly up-regulated, but the apoptosis levels in the four groups were not significantly different. The YAP, TEADs1-4, p-PI3K, and p-AKT1 expressions in the mutant FGFR2 groups were higher than the corresponding expressions in the control groups, and the results of the rescue experiments showed a reverse expression tendency, which further confirmed the effects of the FGFR2 mutations in the dura cells on the proliferation of the osteoblasts and the underlying possible mechanisms. CONCLUSION: Our studies suggest that the Crouzon mutations (C278F- and C342Y-) of FGFR2 in dura cells can enhance osteoblast proliferation and differentiation and might influence the pathogenesis of craniosynostosis by affecting the Hippo/YAP-PI3K-AKT proliferation signaling pathway.

Surgical outcome and patient satisfaction after Z-epicanthoplasty and blepharoplasty.

AIM: To evaluate surgical outcomes of modified Z-epicanthoplasty with blepharoplasty that we previously reported from the patient's perspective using patient-reported outcome measures (PROMs) and patient satisfaction scores. METHODS: A total of patients (n=180) who underwent the surgery between January 2013 and June 2016 were randomly selected. Standardized patient satisfaction forms (total score, 40) and validated PROMs questionnaires (total score, 12) were sent to patients for completion. PROMs assesses the severity of scarring, pain and asymmetry, as well as functional and appearance issues. RESULTS: All patients were female, ranging from 18 to 35 years old (mean=24). The response rate was 73.3% (n=132). The majority of patients reported good or excellent outcomes based on PROM analysis. Patients reported minimum or non-visible scarring at both the double eyelid surgical scar (85.6%) and the inner canthus (80.3%). Issues concerning function and appearance were minimal as 80.3% reported satisfaction with both domains. Notably, the majority of patients reported either a high or very high satisfaction rate to yield a mean score of 104 out of 120 (P<0.05). CONCLUSION: Integration of our modified Z-epicanthoplasty with blepharoplasty produces good outcomes based on PROM results, which shows a positive linear relationship with patient satisfaction scores.