Human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells (MSCs) derived from dental and craniofacial tissues that exhibit high potential for differentiation into osteoblasts. Recently, microRNAs (miRNAs) have been established to play important roles in MSC osteogenesis. In the current study, we report that miR-21 was down-regulated in osteogenically differentiated PDLSCs. Overexpression of miR-21 significantly inhibited osteogenesis of hPDLSC, whereas its inhibition demonstrated the opposite effects. Furthermore, SMAD family member 5 (Smad5) was predicted to be a downstream target of miR-21 and was shown to undergo up-regulation in PDLSCs induced toward osteogenesis. Moreover, Smad5 and Runx2, which are the critical transcription factors in osteogenic differentiation, were predicted to be targets of miR-21. Suppression of miR-21 expression increased the level of Smad5 in vitro and during in vivo transplantation experiments. Furthermore, suppression of Smad5 inhibited osteogenic differentiation and decreased the protein level of Runx2. Taken together, these results suggested that miR-21 be mechanistically implicated in the regulation of osteogenic differentiation of hPDLSCs by targeting Smad5.

These authors equally contributed to this work.Keywords: B55a, checkpoint recovery, DNA damage, Plk1, PP2AIn addition to governing mitotic progression, Plk1 also suppresses the activation of the G2 DNA damage checkpoint and promotes checkpoint recovery. Previous studies have shown that checkpoint activation after DNA damage requires inhibition of Plk1, but the underlying mechanism of Plk1 regulation was unknown. In this study we show that the specific phosphatase activity toward Plk1 Thr-210 in interphase Xenopus egg extracts is predominantly PP2A-dependent, and this phosphatase activity is upregulated by DNA damage. Consistently, PP2A associates with Plk1 and the association increases after DNA damage. We further revealed that B55a, a targeting subunit of PP2A and putative tumor suppressor, mediates PP2A/Plk1 association and Plk1 dephosphorylation. B55a and PP2A association is greatly strengthened after DNA damage in an ATM/ATR and checkpoint kinase-dependent manner. Collectively, we report a phosphatase-dependent mechanism that responds to DNA damage and regulates Plk1 and checkpoint recovery.

To construct a saliva-based caries risk assessment model, saliva samples from 176 severe early childhood caries (S-ECC) children and 178 healthy (H) children were screened by real-time PCR-based quantification of the selected species, including Streptococcus mutans, Prevotella pallens, Prevotella denticola and Lactobacillus fermentum. Host factors including caries status, dmft indices, age, gender, and geographic origin were assessed in their influence on abundance of the targeted species, which revealed host caries status as the dominant factor, followed by dmft indices (both P < 0.01). Moreover, levels of S. mutans and P. denticola in the S-ECC group were significantly higher than those in the healthy group (P < 0.001 for S. mutans and p < 0.01 for P. denticola). Interestingly, the co-occurrence network of these targeted species in the S-ECC group differed from that from the healthy group. Finally, based on the combined change pattern of S. mutans and P. pallens, we constructed an S-ECC diagnosis model with an accuracy of 72%. This saliva-based caries diagnosis model is of potential value for circumstances where sampling dental plague is difficult. Early childhood caries (ECC) is defined as the presence of one or more decayed, missing, or filled tooth surfaces in the primary dentition in children of 71 months or younger 1. Severe early childhood caries (S-ECC), an extraordinary form of ECC, is defined as the presence of decayed, missing, or filled score surfaces of either ≥4 (age 3 years), ≥5 (age 4 years), or ≥6 (age 5 years) 2. In USA, 23% of children between the ages of 2 and 5 are affected by ECC 3. In China, fresh reports from the Fourth National Oral Health Survey showed that over 70% of 5-year-old children carry dental caries in primary teeth 4. Unfortunately, childhood caries are wide-ranging, rapid-progressing and irreversible 5. Besides, severe caries can cause pulpal infection, as well as varieties of adverse physical and psychological effects, thus it affects children's development while posing a substantial economic burden on both families and society 6-8. Therefore, preventive measures and early diagnosis of ECC or S-ECC are of vital clinical and social importance. Many studies have shown that caries is a multifactorial disease 9,10 and pathogenic bacteria are the main cause of disease occurrence and progression 11. Streptococcus mutans (S. mutans) has been considered as a cariogenic bacterial agent in children 12-15 , due to its aciduric and acidogenic properties 16. Apart from this, Lactobacillus spp. was also linked to caries development and progression 16-18. Positive associations between certain Lactobacillus spp. (especially Lactobacillus fermentum) and the hard tissue changes were revealed in the process of caries progression 19,20. In addition, our past pyrosequencing of oral and plaque microbiota unveiled Prevotella spp's close relationship with caries, in both cross-sectional and longitudinal studies 21,22. Specifically, we proposed a caries

Abstract:Objective: The purpose of this study was to evaluate three-dimensional (3D) dehiscence of upper anterior alveolar bone during incisor retraction and intrusion in adult patients with maximum anchorage. Methods: Twenty adult patients with bimaxillary dentoalveolar protrusion had the four first premolars extracted. Miniscrews were placed to provide maximum anchorage for upper incisor retraction and intrusion. A computed tomography (CT) scan was performed after placement of the miniscrews and treatment. The 3D reconstructions of pre-and post-CT data were used to assess the dehiscence of upper anterior alveolar bone. Results: The amounts of upper incisor retraction at the edge and apex were (7.64±1.68) and (3.91±2.10) mm, respectively, and (1.34±0.74) mm of upper central incisor intrusion. Upper alveolar bone height losses at labial alveolar ridge crest (LAC) and palatal alveolar ridge crest (PAC) were 0.543 and 2.612 mm, respectively, and the percentages were (6.49±3.54)% and (27.42±9.77)%, respectively. The shape deformations of LAC-labial cortex bending point (LBP) and PAC-palatal cortex bending point (PBP) were (15.37±5.20)° and (6.43±3.27)°, respectively. Conclusions: Thus, for adult patients with bimaxillary protrusion, mechanobiological response of anterior alveolus should be taken into account during incisor retraction and intrusion. Pursuit of maximum anchorage might lead to upper anterior alveolar bone loss.