LncRNA HOTAIRM1 promotes dental follicle stem cell-mediated bone regeneration by regulating HIF-1α/KDM6/EZH2/H3K27me3 axis.

Large bone defect reconstruction undergoes hypoxia and remains a major practical challenge. Bone tissue engineering with a more promising stem cell source facilitates the development of better therapeutic outcomes. Human dental follicle stem cells (hDFSCs) with superior multipotency, osteogenic capacity, and accessibility have been proven a promising cell source for bone regeneration. We previously identified a novel long noncoding RNA (lncRNA), HOTAIRM1, to be highly expressed in hDFSCs. Here we found that HOTAIRM1 overexpressed hDFSCs promoted bone regeneration in rat critical-size calvarial defect model. Mechanically, HOTAIRM1 was induced in hDFSCs under hypoxic conditions and activated HIF-1α. RNA-sequencing analysis indicated that HOTAIRM1 upregulated oxygen-sensing histone demethylases KDM6A/B and suppressed methyltransferase EZH2 via targeting HIF-1α. The osteogenic differentiation of hDFSCs was accompanied with demethylation of H3K27, and HOTAIRM1 overexpression decreased the distribution of H3K27me3 in osteogenic genes, including ALP, M-CSF, Wnt-3a, Wnt-5a, Wnt-7a, and ß-catenin, thus promoted their transcription. Our study provided evidence that HOTAIRM1 upregulated KDM6A/B and inhibited EZH2 in a HIF-1α dependent manner to enhance the osteogenesis of hDFSCs. HOTAIRM1-mediated hDFSCs may serve as a promising therapeutic approach to promote bone regeneration in clinical practice.

Three-dimensional evaluation of soft tissues in hyperdivergent skeletal class II females in Guangdong.

OBJECTIVES: To establish the three-dimensional facial soft tissue morphology of adolescent and adult females in the Guangdong population and to study the morphological characteristics of hyperdivergent skeletal class II females in Guangdong compared with that of normodivergent class I groups. MATERIALS AND METHODS: The 3dMDface system was used to capture face scans of 160 patients, including 45 normal and 35 hyperdivergent skeletal class II adolescents (aged 11-14 years old) and 45 normal and 35 hyperdivergent skeletal class II adults (aged 18-30 years old). Thirty-two soft tissue landmarks were mapped, and 21 linear, 10 angular and 17 ratio measurements were obtained by 3dMDvultus analysis software. Data were assessed with a t-test of two independent samples between the normal adolescent and adult groups and between the normal and hyperdivergent skeletal class II groups. RESULTS: The linear measurements of the Guangdong adult females were larger than those of the adolescents in both Class I and Class II groups. However, the angular and ratio measurements had no significant difference. The vertical linear measurements were higher and the sagittal and transverse linear measurements were smaller in the hyperdivergent class II group (p < 0.05). The soft tissue ANB angle, chin-lip angle, and mandibular angle were significantly larger and the soft tissue facial convexity angle and nasal convexity angle were significantly smaller in the hyperdivergent class II group (p < 0.05). Additionally, there were significant differences in the ratio measurements between the hyperdivergent class II groups and the control groups (p < 0.05). CONCLUSIONS: The three-dimensional facial morphology of Guangdong adolescent and adult females was acquired. The facial soft tissue measurements of the adults were higher in the three dimensions except for the facial convexity and proportional relationships which were similar, suggesting that the growth pattern remained the same. The three-dimensional facial soft tissue features of hyperdivergent skeletal class II were characterized by the terms "long, convex, and narrow". Three-dimensional facial measurements can reflect intrinsic hard tissue characteristics.