The Teaching of Personalized Dentistry in North American Dental Schools: Changes from 2014 to 2017.

The aim of this study was to assess the development of personalized dentistry in the curricula of North American dental schools from 2014 to 2017. In 2014, a web-based survey on personalized medicine/dentistry (PM/PD) was distributed to academic deans of all U.S. (n=65) and Canadian (n=10) dental schools with graduating classes. The results (n=42; 56% response rate) showed that few schools had plans for implementation of PM/PD at the time, even though the majority of respondents reported feeling that PM/PD should be taught in the curriculum and will impact clinical practice in the future. A three-year followup survey in 2017, sent to the same 75 schools, was designed to reassess the teaching/practice of PM/PD in dental schools in both didactic and clinical curricula. In the results of the 2017 survey (n=30; 40% response rate), the majority of respondents reported feeling that PM/PD should be taught in dental curricula. However, while most respondents indicated their schools did not teach PM/PD as a portion of their didactic curricula, they reported that specific pertinent PM/PD topics were taught as part of other courses in their curricula. The 2017 survey also evaluated the use of seven genetics-based and eight non-genetics-based PM/PD diagnostics in the schools' clinical curricula. Overall, non-genetics-based diagnostics were used more often than genetics-based diagnostics, and the use of genetics-based diagnostics was more prevalent in postgraduate than predoctoral clinics. Personalized dentistry will inevitably be part of the dental professional's future and should be reflected in basic science research, clinical settings, and dental school curricula in both predoctoral and postgraduate programs.

Inhibition of matrix metalloproteinase-mediated periodontal bone loss in rats: a comparison of 6 chemically modified tetracyclines.

BACKGROUND: Chemically modified tetracyclines (CMTs), devoid of antimicrobial activity, inhibit pathologically elevated collagenase activity both in vivo and in vitro. In the current study, doxycycline and 5 different CMTs were tested to prevent matrix metalloproteinase (MMP)-dependent periodontal tissue breakdown in an animal model of periodontitis. METHODS: Adult male rats received intragingival injections with either 10 microl of physiologic saline or Escherichia coli endotoxin (1 mg/ml) every other day for 6 days and were distributed into 8 treatment groups (12 rats/group): saline (S), endotoxin alone (E), E + CMT-1, E + CMT-3, E + CMT-4, E + CMT-7, E + CMT-8, and doxycycline. All animals were treated daily with 1 ml of 2% carboxymethyl cellulose (CMC) alone or containing one of the above-mentioned CMTs (2 mg/day) orally. The gingival tissues were removed, extracted, and assayed for gelatinase (GLSE). Some rat maxillary jaws from each treatment group were fixed in buffered formalin and processed for histology and immunohistochemistry for the cytokines tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, and MMP-2 and MMP-9. RESULTS: Endotoxin injection induced elevated GLSE activity (functional assay and osteoclast-mediated bone resorption), the former identified as predominantly MMP-9 (92 kDa GLSE) by gelatin zymography. All 6 tetracyclines (2 mg/day) inhibited periodontal breakdown in the following order of efficacy: CMT-8 > CMT- 1 > CMT-3 > doxycycline > CMT-4 > CMT-7. Immunohistochemistry was positive for TNF, IL-1, and IL-6 in the inflammatory cells from untreated endotoxin rat tissues, whereas treatment with CMTs decreased the number of immuno-positive stained cells for cytokines and MMPs. The in vivo efficacy of these drugs varied with CMT structure and was significantly correlated with bone resorption: r2 = -0.77, P<0.01; gelatinase inhibitory activity: r2 = -0.84, P <0.01; and serum drug concentrations. CONCLUSION: Since both conventional (antimicrobial) and non-antimicrobial tetracyclines inhibited periodontal bone resorption induced by endotoxin injection, MMP-mediated bone loss in this model can be prevented by inhibition of MMPs.

Blocking Periodontal Disease Progression by Inhibiting Tissue-Destructive Enzymes: A Potential Therapeutic Role for Tetracyclines and Their Chemically-Modified Analogs.

Tetracyclines (TCs) have wide therapeutic usage as antimicrobial agents; these drugs (e.g., minocycline, doxycycline) remain useful as adjuncts in periodontal therapy. However, TCs also have non-antimicrobial properties which appear to modulate host response. In that regard, TCs and their chemically-modified analogs (CMTs) have been shown to inhibit the activity of the matrix metalloproteinase (MMP), collagenase. The activity of this enzyme appears crucial in the destruction of the major structural protein of connective tissues, collagen. Such pathologic collagenolysis may be a common denominator in tissue destructive diseases such as rheumatoid and Osteoarthritis, diabetes mellitus, bullous dermatologic diseases, corneal ulcers, and periodontitis. The mechanisms by which TCs affect and, possibly, diminish bone resorption (a key event in the pathogenesis of periodontal and other diseases) are not yet understood. However, a number of possibilities remain open for investigation including the following: TCs may 1) directly inhibit the activity of extracellular collagenase and other MMPs such as gelatinase; 2) prevent the activation of its proenzyme by scavenging reactive oxygen species generated by other cell types (e.g. PMNs, osteoclasts); 3) inhibit the secretion of other collagenolytic enzymes (i.e. lysosomal cathepsins); and 4) directly affect other aspects of osteoclast structure and function. Several recent studies have also addressed the therapeutic potential of TCs and CMTs in periodontal disease. These drugs reduced excessive gingival collagenase activity and severity of periodontal breakdown in rats infected with Porphyromonas gingivalis and in diabetic rats. Furthermore, the latter drug (CMT) was not associated with the emergence of TC-resistant microorganisms. In human clinical trials, low-dose doxycycline therapy substantially reduced collagenase activity in the gingiva and GCF, and prevented the loss of attachment in adult periodontitis. Clearly, the non-antimicrobial properties of TCs have enormous medical and dental therapeutic potential since these drugs can inhibit the activity of MMPs and their degradation of non-osseous and osseous connective tissues. J Periodontol 1993; 64:819-827.