LncRNA TUG1 positively regulates osteoclast differentiation by targeting v-maf musculoaponeurotic fibrosarcoma oncogene homolog B.

Osteoclast differentiation-mediates bone resorption is the key biological basis of orthodontic treatment while the specific mechanism of osteoclastogenesis remains unclear. This study aims to explore the underlying mechanism of the osteoclast differentiation from the perspective of long non-coding RNA (LncRNA). In the present study, the osteoclast differentiation of CD14+ peripheral blood mononuclear cells (PBMCs) was induced by recombinant human macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL), and LncRNA TUG1 expression was dramatically elevated during this process. Functionally, the silence of TUG1 in CD14+ PBMCs decreased tartrate-resistant acid phosphatase (TRAP)-positive cell numbers and the protein levels of TRAP, nuclear factor of activated T cell c1 (NFATc1), and osteoclast-associated receptor (OSCAR), whereas increased V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) protein level. The subsequent experiments confirmed that TUG1 lessened the MafB protein level via accelerating its degradation. Then, the interference of MafB reversed the inhibitory effect of si-TUG1 on osteoclastogenesis, including increased the TRAP-positive cell numbers and up-regulated the protein levels of osteoclast markers. Finally, the in vivo experiments displayed that the increased TUG1 levels could promote tooth movement and bone resorption via facilitating osteoclast differentiation in the rat model of orthodontic tooth movement. In summary, TUG1 overexpressed during the process of osteoclast differentiation and positively regulated osteoclast differentiation by targeting MafB.

New insights from GWAS for the cleft palate among han Chinese population

BACKGROUND: Genome wide association studies (GWAS) already have identified tens of susceptible loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, whether these loci associated with nonsyndromic cleft palate only (NSCPO) remains unknown. MATERIAL AND METHODS: In this study, we replicated 38 SNPs (Single nucleotide polymorphisms) which has the most significant p values in published GWASs, genotyping by using SNPscan among 144 NSCPO trios from Western Han Chinese. We performed the transmission disequilibrium test (TDT) on individual SNPs and gene-gene (GxG) interaction analyses on the family data; Parent-of-Origin effects were assessed by separately considering transmissions from heterozygous fathers versus heterozygous mothers to affected offspring. RESULTS: Allelic TDT results showed that T allele at rs742071 (PAX7) (p = 0.025, ORtransmission=3.00, 95%CI: 1.09- 8.25) and G allele at rs2485893 (10kb 3' of SYT14) were associated with NSCPO (p = 0.0036, ORtransmission= 0.60, 95%CI: 0.42-0.85). Genotypic TDT based on 3 pseudo controls further confirmed that rs742071 (p-value=0.03, ORtransmission=3.00, 95%CI: 1.09-8.25) and rs2485893 were associated with NSCPO under additive model (p-value= 0.02, ORtransmission= 0.66, 95%CI: 0.47-0.92). Genotypic TDT for epistatic interactions showed that rs4844913 (37kb 3' of DIEXF) interacted with rs11119388 (SYT14) (p-value=1.80E-08) and rs6072081 (53kb 3' of MAFB) interacted with rs6102085 (33kb 3' of MAFB) (p-value=3.60E-04) for NSCPO, suggesting they may act in the same pathway in the etiology of NSCPO. CONCLUSIONS: In this study, we found that rs742071 and rs2485893 were associated NSCPO from Han Chinese population; also, interactions of rs4844913:rs11119388 and rs6072081:rs6102085 for NSCPO were identified, genegene interactions have been proposed as a potential source of the remaining heritability, these findings provided new insights of the previous GWAS

Expression of RUNX2 and MDM21 in rats with periodontitis under chronic intermittent hypoxia.

OBJECTIVE: To discuss the expression of RUNX2 and MDM21 in rats with periodontitis under the chronic intermittent hypoxia. METHODS: A total of 32 SD healthy rats were randomly divided into four groups, with 8 rats in each group. The molecular biological techniques of immunohistochemistry, RT-PCR and Western blotting were employed to detect the effect of different hypoxia time (0, 6, 12, 24 and 48 h) and different concentrations of hypoxia (0.000, 0.001, 0.010, 0.060 and 0.100 ppm) on the expression of RUNX2 and MDM21 in rats of four groups. RESULTS: The expression of RUNX2 and MDM21 in each group was significantly higher than the one at other concentrations when the concentration was 0.010 ppm, with the statistical difference (P < 0.05). The expression of RUNX2 and MDM21 was that normoxic control group > normoxic periodontitis group > hypoxia control group > hypoxia periodontitis group under the action with the concentration of 0.010 ppm for 12 h, but there was no significant difference for the comparison among groups (P > 0.05). CONCLUSIONS: The condition of chronic intermittent hypoxia can reduce the expression of RUNX2 and MDM21 in rats with periodontitis and aggravate the damage of periodontal bone.