Research Spotlight

Jani, P., H. Zhang, M. D. Benson and C. Qin (2019). “Noggin inhibition of mouse dentinogenesis.” J Oral Biosci Dec 17. pii: S1349-0079(19)30242-7. [Epub ahead of print].

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OBJECTIVES: The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts. METHODS: We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfss signaling in the same tissues. RESULTS: Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphopritein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth. CONCLUSIONS: The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfss ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.

Gao, X., R. Y. L. Tsai, J. Ma, P. K. Bhupal, X. Liu, D. Liang and H. Xie (2020). “Determination and validation of mycophenolic acid by a UPLC-MS/MS method: Applications to pharmacokinetics and tongue tissue distribution studies in rats.” J Chromatogr B Analyt Technol Biomed Life Sci 1136: 121930.

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Mycophenolic acid (MPA) has being used clinically for organ rejection prophylaxis. Recent studies have revealed that MPA can also act as a chemo-sensitizing agent when used in combination with various chemotherapeutic agents in a cancer type-specific manner, including with oxaliplatin on oral squamous cell carcinoma (OSCC) cells. To prepare for the analysis of a novel drug delivery route for MPA absorption via oral mucosa as a potential therapeutic product, it is essential to develop and validate a highly sensitive analytical method for the quantification of MPA in biological samples for pharmacokinetic and tissue distribution studies. Herein, we report a sensitive, specific and reproducible UPLC-MS/MS method to do so. Blank rat plasma or tongue tissue homogenates coupled with griseofulvin, as internal standard, was used for generating standard curves ranging from 0.5 to 1000 ng/mL (r > 0.9990) for both plasma and tongue tissue homogenates. The chromatographic separation was achieved by a reverse phase ACE Excel 2 Super C18 column with a flow rate of 0.4 mL/min under gradient elution. Mass detection was performed under positive ionization electrospray. Inter- and intra-day accuracy and precision of the assay were

Cabello-Dominguez, G., J. Perez-Lopez, B. Veiga-Lopez, D. Gonzalez and M. Revilla-Leon (2019). “Maxillary zirconia and mandibular composite resin-lithium disilicate-modified PEEK fixed implant-supported restorations for a completely edentulous patient with an atrophic maxilla and mandible: A clinical report.” J Prosthet Dent Dec 20. pii: S0022-3913(19)30663-8. [Epub ahead of print].

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Bimaxillary implant-supported restorations for edentulous patients must include a comprehensive diagnosis, treatment plan, and careful selection of the restorative materials. The present clinical report described a completely edentulous patient rehabilitated with a zirconia framework with a facial ceramic veneer on the maxillary arch and a modified polyetheretherketone (PEEK) framework with gingival composite resin and cemented lithium disilicate crowns on the mandibular arch. The rationale for this combination of restorative materials is reviewed.

Bai, Q., J. Shao, J. Cao, X. Ren, W. Cai, S. Su, S. George, Z. Tan, W. Zang and T. Dong (2020). “Protein kinase C-alpha upregulates sodium channel Nav1.9 in nociceptive dorsal root ganglion neurons in an inflammatory arthritis pain model of rat.” J Cell Biochem 121(1): 768-778.

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Previous studies have found that increased expression of Nav1.9 and protein kinase C (PKC) contributes to pain hypersensitivity in a couple of inflammatory pain models. Here we want to observe if PKC can regulate the expression of Nav1.9 in dorsal root ganglion (DRG) in rheumatoid arthritis (RA) pain model. A chronic knee joint inflammation model was produced by intra-articular injection of the complete Freund’s adjuvant (CFA) in rats. Nociceptive behaviors including mechanical, cold, and heat hyperalgesia were examined. The expression of Nav1.9 and PKCalpha in DRG was detected by a quantitative polymerase chain reaction, Western blot, and immunofluorescence. The in vitro and in vivo effects of a PKC activator (phorbol 12-myristate 13-acetate [PMA]) and a PKC inhibitor (GF-109203X) on the expression of Nav1.9 were examined. Moreover, the effects of PKC modulators on nociceptive behaviors were studied. Increased mechanical, heat, and cold sensitivity was observed 3 to 14 days after CFA injection. Parallel increases in messenger RNA and protein expression of Nav1.9 and PKCalpha were found. Immunofluorescence experiments found that Nav1.9 was preferentially colocalized with IB4+DRG neurons in RA rats. In cultured DRG neurons, PMA increased Nav1.9 expression while GF-109203X prevented the effect of PMA. PMA increased Nav1.9 expression in naive rats while GF-109203X decreased Nav1.9 expression in RA rats. In naive rats, PMA caused mechanical and cold hyperalgesia. On the other hand, GF-109203X attenuated mechanical and cold hyperalgesia in RA-pain model. Nav1.9 might be upregulated by PKCalpha in DRG, which contributes to pain hypersensitivity in CFA-induced chronic knee joint inflammation model of RA pain.

Azarpazhooh, A., A. R. Diogenes, A. F. Fouad, G. N. Glickman, M. K. Kang, A. Kishen, L. Levin, R. S. Roda, C. M. Sedgley, F. R. Tay and K. M. Hargreaves (2020). “Insights into the January 2020 Issue of the Journal of Endodontics.” J Endod 46(1): 1-2.

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Welcome to the January 2020 issue of the Journal of Endodontics ( JOE ). Here, we share some of our favorite articles that were published in this issue of the journal. We hope you look forward to reading these and other articles in JOE. [Excerpt from Article].