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Periodontitis is a highly prevalent infectious disease associated genetically with coronary heart disease (CHD). The effects of proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of CHD, on periodontitis have not been studied to date. Here, we found that PCSK9 expression was increased in periodontitis patients and Porphyromonas gingivalis (Pg)-infected mice. Loss of PCSK9 attenuated Pg-induced periodontal bone loss in mice. First, PCSK9 deficiency reduced the release of inflammation-associated cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 1ß, in vitro and in vivo. Second, its deficiency enhanced Pg and endotoxin clearance during Pg invasion in part by upregulating CD36 and low-density lipoprotein receptor (LDLR), respectively. However, after berberine treatment, periodontal bone regeneration in the PCSK9 knockout group was significantly lower than that in wild-type. This was because PCSK9 overexpression promoted osteogenic differentiation of periodontal ligament stem cells (PDLCs) prechallenged by TNF-α. Furthermore, PCSK9 could rescue PDLC osteogenesis by repressing the NF-κB signaling pathway by interacting with TRAF2. These results suggest that PCSK9 may be a potent drug target for treating periodontitis.

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Endochondral ossification is an essential skeletal development process which is strongly linked to chondrocyte differentiation. DNA damage-inducible transcript 3 (Ddit3), a member of the CCAAT/enhancer-binding protein family of transcription factors, is highly expressed in the cartilage plate. However, the role of DNA damage-inducible transcript 3 in chondrocyte differentiation remains to be investigated. Immunofluorescent staining was used to detect Ddit3 expression in the mouse growth plate and in the mouse chondroprogenitor cell line ATDC5. A lentivirus system was employed to overexpress Ddit3 and silence its endogenous expression in ATDC5 cells. The differentiation abilities of ATDC5 cells were examined through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and chondrogenic and hypertrophic-related staining. Western blot analysis was performed to detect the protein expression of sex-determining region Y-type high-mobility group box 9 and CCAAT/enhancer-binding protein ß. Ddit3 was expressed in the proliferative and hypertrophic zones of the mouse growth plate. Ddit3 knockdown significantly enhanced the expression of chondrogenic and hypertrophic markers, whereas Ddit3 overexpression decreased the expression of these markers. This finding was also evidenced by Alcian blue staining, proteoglycan synthesis and alkaline phosphatase assay. Additionally, Ddit3 down-regulation significantly led to Sox9 up-regulation. These results suggest that Ddit3 suppresses the differentiation of ATDC5 cells. The function of Ddit3 might partially be regulated by Sox9 expression during chondrogenic and hypertrophic differentiation.

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Intracellular thiols play vital roles in living systems, and their in situ monitoring is of great importance. Here, we report on a bioorthogonal chemistry based fluorescent probe, which is capable of monitoring intracellular thiols in living cells for up to 36 hours with an obvious blue-to-green fluorescence change.

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INTRODUCTION: The aim of this study was to investigate whether SIRT6 is expressed in human dental pulp as well as the effect of SIRT6 on proliferation and odontoblastic differentiation of human dental pulp cells (HDPCs). METHODS: Immunohistochemical and immunocytochemical assays were used to detect the expression of SIRT6 in human dental pulp tissue and HDPCs. To determine the effect of SIRT6 on odontoblast differentiation, HDPCs with loss (HDPCs SIRT6 knockdown) and gain (HDPCs SIRT6 overexpression) of SIRT6 function were developed, and their proliferation ability was examined. Odontogenic differentiation of HDPCs was determined by alkaline phosphatase (ALP) activity, ALP-positive cell staining, alizarin red staining, and von Kossa staining. Mineralization-related genes, including ALP, dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1, were determined by real-time quantitative polymerase chain reaction. Western blot analysis was performed to detect the expression of DSPP protein. RESULTS: SIRT6 was found in the dental pulp tissue and HDPCs. SIRT6 knockdown decreased ALP activity in HDPCs; calcium nodule formation ability; and the expression of mineralization-related genes such as ALP, DSPP, and DMP1, whereas these were increased with the overexpression of SIRT6. CONCLUSIONS: SIRT6 is expressed in human dental pulp and participates in the odontoblast differentiation of HDPCs.

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PURPOSE: The aim of this study was to evaluate the long-term failure rates of short dental implants (≤ 10 mm) and to analyze the influence of various factors on implant failure. MATERIALS AND METHODS: The PubMed and Cochrane Library databases were consulted for follow-up studies published between the years 1980 and 2009. For those studies that met the inclusion and exclusion criteria, data concerning the number of implants (≤ 10 mm) placed and lost and any related risk factors were gathered in tables and subjected to analysis. Univariate and multivariate analyses were performed. RESULTS: The heterogeneity and low quality of the included studies made meta-analysis impossible. A total of 35 human studies fulfilled the criteria. The studies included 14,722 implants, of which 659 failed. The total failure rate was 4.5%. The failure rates of implants with lengths of 6, 7, 7.5, 8, 8.5, 9, and 10 mm were 4.1%, 5.9%, 0%, 2.5%, 3.2%, 0.6%, and 6.5%, respectively. A majority (57.9%) of failures occurred before prosthesis connection. There was no statistically significant difference between the failure rates of short dental implants and standard implants or between those placed in a single stage and those placed in two stages (multivariate analysis). There was a tendency toward higher failure rates for the maxilla and for dental implants with a machined surface compared with the mandible and dental implants with a rough surface, respectively. CONCLUSIONS: Among the risk factors examined, most failures of short implants can be attributed to poor bone quality in the maxilla and a machined surface. Although short implants in atrophied jaws can achieve similar long-term prognoses as standard dental implants with a reasonable prosthetic design according to this review, stronger evidence is essential to confirm this finding.

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