Role of Mechanotransduction in Periodontal Homeostasis and Disease.

Novel findings broaden the concept of mechanotransduction (MT) in biophysically stimulated tissues such as the periodontium by considering nuclear MT, convergence of intracellular MT pathways, and mechanoresponsive cotranscription factors such as Yes-associated protein 1 (YAP1). Regarding periodontal disease, recent studies have elucidated the role of bacterial gingipain proteases in disturbing the barrier function of cadherins, thereby promoting periodontal inflammation. This leads to dysregulation of extracellular matrix homeostasis via proteases and changes the cell's biophysical environment, which leads to alterations in MT-induced cell behavior and loss of periodontal integrity. Newest experimental evidence from periodontal ligament cells suggests that the Hippo signaling protein YAP1, in addition to integrin-FAK (focal adhesion kinase) mechanosignaling, also regulates cell stemness. By addressing mechanosignaling-dependent transcription factors, YAP1 is involved in osteogenic and myofibroblast differentiation and influences core steps of autophagy. Recent in vivo evidence elucidates the decisive role of YAP1 in epithelial homeostasis and underlines its impact on oral pathologies, such as periodontitis-linked oral squamous cell carcinogenesis. Here, new insights reveal that YAP1 contributes to carcinogenesis via overexpression rather than mutation; promotes processes such as apoptosis resistance, epithelial-mesenchymal transition, or metastasis; and correlates with poor prognosis in oral squamous cell carcinoma. Furthermore, YAP1 has been shown to contribute to periodontitis-induced bone loss. Mechanistically, molecules identified to regulate YAP1-related periodontal homeostasis and disease include cellular key players such as MAPK (mitogen-activated protein kinase), JNK (c-Jun N-terminal kinase), Rho (Ras homologue) and ROCK (Rho kinase), Bcl-2 (B-cell lymphoma 2), AP-1 (activator protein 1), and c-myc (cellular myelocytomatosis). These findings qualify YAP1 as a master regulator of mechanobiology and cell behavior in human periodontal tissues. This review summarizes the most recent developments in MT-related periodontal research, thereby offering insights into outstanding research questions and potential applications of molecular or biophysical strategies aiming at periodontal disease mitigation or prevention.

Evaluation of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry in comparison to 16S rRNA gene sequencing for species identification of nonfermenting bacteria.

Nonfermenting bacteria are ubiquitous environmental opportunists that cause infections in humans, especially compromised patients. Due to their limited biochemical reactivity and different morphotypes, misidentification by classical phenotypic means occurs frequently. Therefore, we evaluated the use of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) for species identification. By using 248 nonfermenting culture collection strains composed of 37 genera most relevant to human infections, a reference database was established for MALDI-TOF MS-based species identification according to the manufacturer's recommendations for microflex measurement and MALDI BioTyper software (Bruker Daltonik GmbH, Leipzig, Germany), i.e., by using a mass range of 2,000 to 20,000 Da and a new pattern-matching algorithm. To evaluate the database, 80 blind-coded clinical nonfermenting bacterial strains were analyzed. As a reference method for species designation, partial 16S rRNA gene sequencing was applied. By 16S rRNA gene sequencing, 57 of the 80 isolates produced a unique species identification (>or=99% sequence similarity); 11 further isolates gave ambiguous results at this threshold and were rated as identified to the genus level only. Ten isolates were identified to the genus level (>or=97% similarity); and two isolates had similarity values below this threshold, were counted as not identified, and were excluded from further analysis. MALDI-TOF MS identified 67 of the 78 isolates (85.9%) included, in agreement with the results of the reference method; 9 were misidentified and 2 were unidentified. The identities of 10 randomly selected strains were 100% correct when three different mass spectrometers and four different cultivation media were used. Thus, MALDI-TOF MS-based species identification of nonfermenting bacteria provided accurate and reproducible results within 10 min without any substantial costs for consumables.