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Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown. Herein, we investigated the roles of RUNX2-miR-31-SATB2 in DFCs from patients with CCD (DFCs-CCD) to advance our understanding regarding physical tooth eruption. We identified a novel mutation on exon 5 (c.634T>G, p.T212P) in RUNX2 via exome sequencing in the CCD patient with typical clinical presentations. Compared with DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated SATB2. Lower ratios of RANKL/OPG and RANKL/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs-CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-31 knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-31 overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption. Together, these results suggest that RUNX2 mutation/haploinsufficiency disturbs osteoclast-inductive signaling in DFCs, which may be responsible for delayed tooth eruption in CCD patients. Manipulation of the RUNX2-miR-31-SATB2 loop may be a potential way to facilitate tooth eruption in CCD patients.

ObjectivesTonsillotomy has gained popular acceptance as an alternative to the traditional tonsillectomy in the management of sleep-disordered breathing in children. Many studies have evaluated the outcomes of the two techniques, but uncertainty remains with regard to the efficacy and complications of tonsillotomy versus a traditional tonsillectomy. This study was designed to investigate the efficacy and complications of tonsillotomy versus tonsillectomy, in terms of the short- and long-term results.MethodsWe collected data from electronic databases including MEDLINE, EMBASE, and the Cochrane Library. The following inclusion criteria were applied: English language, children, and prospective studies that directly compared tonsillotomy and tonsillectomy in the management of sleep disordered breathing. Subgroup analysis was then performed.ResultsIn total, 10 eligible studies with 1029 participants were included. Tonsillotomy was shown to be advantageous over tonsillectomy in short-term measures, such as a lower hemorrhage rate, shorter operation time, and faster pain relief. In long-term follow-up, there was no significant difference in resolution of upper-airway obstructive symptoms, the quality of life, or postoperative immune function between the tonsillotomy and tonsillectomy groups. The risk ratio of SDB recurrence was 3.33 (95% confidence interval = 1.62 6.82, P = 0.001), favoring tonsillectomy at an average follow-up of 31 months.ConclusionsTonsillotomy may be advantageous over tonsillectomy in the short term measures and there are no significant difference of resolving obstructive symptoms, quality of life and postoperative immune function. For the long run, the dominance of tonsillotomy may be less than tonsillectomy with regard to the rate of sleep-disordered breathing recurrence.

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