A Novel lncRNA Mediates the Delayed Tooth Eruption of Cleidocranial Dysplasia.

Delayed eruption of permanent teeth is a common symptom of cleidocranial dysplasia (CCD). Previous studies have focused on the anomaly of osteogenesis resulting from mutations in the Runt-related transcription factor-2 gene (RUNX2). However, deficiencies in osteoclastogenesis and bone resorption, and the epigenetic regulation mediated by long non-coding (lnc)RNAs in CCD remain to be elucidated. Here, a novel osteoclast-specific lncRNA (OC-lncRNA) was identified during the osteoclast differentiation of RAW 264.7 cells transfected with a RUNX2 mutation expression cassette. We further confirmed that OC-lncRNA positively regulated osteoclastogenesis and bone resorption. The OC-lncRNA promoted the expression of CXC chemokine receptor type 3 (CXCR3) by competitively binding to microRNA (miR)-221-5p. The CXCR3-CXC-motif chemokine ligand 10 (CXCL10) interaction and nuclear factor-κB constituted a positive feedback that positively regulated osteoclastogenesis and bone resorption. These results demonstrate that OC-lncRNA-mediated osteoclast dysfunction via the OC-lncRNA-miR-221-5p-CXCR3 axis, which is involved in the process of delayed tooth eruption of CCD.

Multiple roles of Runt-related transcription factor-2 in tooth eruption: bone formation and resorption.

OBJECTIVE: The aim was to provide a comprehensive review of the current knowledge of the multiple roles of Runt-related transcription factor-2 (RUNX2) in regulating tooth eruption, focusing on the molecular mechanisms regarding tooth eruption mediated by RUNX2. DESIGN: Relevant literatures in PubMed, Medline, and Scopus database were searched, and a narrative review was performed. The multiple roles of RUNX2 in regulating tooth eruption was reviewed and discussed. RESULTS: Aberrant RUNX2 expression leads to disturbed or failed tooth eruption. Tooth eruption involves both the process of bone formation and bone resorption. RUNX2 promotes osteogenesis around the radicular portion of the dental follicle that provides the biological force for tooth eruption through inducing the expression of osteogenesis-related genes in dental follicle cells/osteoblasts. On the other hand, through indirect and direct pathways, RUNX2 regulates osteoclastogenesis and the formation of the eruption pathway. CONCLUSION: RUNX2 exerts a pivotal and complex influence in regulating tooth eruption. This review provides a better understanding of the function of RUNX2 in tooth eruption, which is beneficial to illuminate the precise molecular mechanism of osteogenesis and bone resorption, aiding the development of effective therapy for the failure of tooth eruption.

New Function of RUNX2 in Regulating Osteoclast Differentiation via the AKT/NFATc1/CTSK Axis.

Cleidocranial dysplasia is an autosomal dominant skeletal disorder resulting from RUNX2 mutations. The influence of RUNX2 mutations on osteoclastogenesis and bone resorption have not been reported. To investigate the role of RUNX2 in osteoclast, RUNX2 expression in macrophages (RAW 264.7 cells) was detected. Stable RAW 264.7 cell lines expressing wild-type RUNX2 or mutated RUNX2 (c.514delT, p.172 fs) were established, and their functions in osteoclasts were investigated. Wild-type RUNX2 promoted osteoclast differentiation, formation of F-actin ring, and bone resorption, while mutant RUNX2 attenuated the positive differentiation effect. Wild-type RUNX2 increased the expression and activity of mTORC2. Subsequently, mTORC2 specifically promoted phosphorylation of AKT at the serine 473 residue. Activated AKT improved the nuclear translocation of NFATc1 and increased the expression of downstream genes, including CTSK. Inhibition of AKT phosphorylation abrogated the osteoclast formation of wild-type macrophages, whereas constitutively activated AKT rescued the osteoclast formation of mutant macrophages. The present study suggested that RUNX2 promotes osteoclastogenesis and bone resorption through the AKT/NFATc1/CTSK axis. Mutant RUNX2 lost the function of regulating osteoclast differentiation and bone remodeling, resulting in the defective formation of the tooth eruption pathway and impaction of permanent teeth in cleidocranial dysplasia. This study, for the first time, verifies the effect of RUNX2 on osteoclast differentiation and bone resorption and provides new insight for the explanation of cleidocranial dysplasia.

Enhanced activity of macrophage M1/M2 phenotypes in periodontitis.

OBJECTIVE: Monocytes/macrophages play a key role in mobilizing host defense against microbial infection. The selectivity of gene expression can turn macrophages into M1- or M2-type and the plasticity and differentiation of both M1 and M2 macrophages may play important roles in the development of periodontal disease. Our research aimed to study the association between the ratio of M1/M2 macrophage and inflammatory cytokines IL-1ß, MMP-9, and investigate the expressions of M1-and M2-type macrophages in gingivitis and chronic periodontitis. METHODS: Forty specimens were collected from gingivitis individuals (n=20) and chronic periodontitis (n=20). Probing depth (PD), clinical attachment level (CAL), plaque index (PI) and bleeding on probing (BOP) were recorded. The expressions of M1- and M2-type macrophages are detected with immunohistochemical method and the relative expressions of M1-, M2-type macrophage, IL-1ß and MMP-9 were assayed using real-time polymerase chain reactions. RESULTS: The M1 and M2 peptide were mainly observed in the cytoplasm of gingival connective tissue. The ratio of M1/M2 was significant higher in chronic periodontitis group compared with that in gingivitis one. In addition, the relative expressions of IL-1ß and MMP-9 also increased in periodontitis group and was correlated with the ratios of M1/M2. Meanwhile, PD was positively correlated with ratios of M1/M2. CONCLUSIONS: Periodontal inflammation associates with an enhancement of ratio of M1/M2 phenotypes of macrophages. M1/M2 ratio could provide useful information on the periodontal tissue health status.

A review of the literature: antibiotic usage and its relevance to the infection in periodontal flaps.

OBJECTIVE: This study aimed to investigate the systemic antibiotic usage in the perioperative period of periodontal flaps and its relevance to the infection after surgeries through reviewing the papers of the last decade. MATERIALS AND METHODS: A search was conducted for the studies of randomized clinical trials between 2005 and 2014 that reported periodontal flaps in chronic periodontitis patients. Data were extracted and the rate of the systemic antibiotic use, the infection rate after surgeries and the number needed to treat (NNT) to prevent one infected case were calculated. The impact of antibiotic use and materials used in surgeries on the infection was evaluated. RESULTS: Eighty-three trials were included. Antibiotics were used in 73.7% of the patients and 75.4% of the flaps. Infection occurred in only five flaps where enamel matrix proteins (EMD) or EMD + bone grafts were used in intrabony defects. Only 0.170% of the surgeries got infected in total. When all kinds of surgeries were included for analysis, the infection rate was 0.073% for the surgeries using antibiotics, which was lower than the infection rate 0.693% for the surgeries not using antibiotics (p < .05). The infection rate was very low in general. NNT was 203 when all the surgeries were included for analysis. Therefore, the difference of the infection rates between using antibiotics and not might lack clinical significance. CONCLUSIONS: Considering the very low incidence of the infection and the disadvantages of the systemic antibiotic use, we suggest not using systemic antibiotics in the perioperative period of periodontal flaps to prevent infection.