MicroRNAs (miRNAs) are small RNA molecules of 21–25 nucleotides that regulate cell behavior through inhibition of translation from mRNA to protein, promotion of mRNA degradation and control of gene transcription. In this study, we investigated the miRNA expression signatures of cell cultures undergoing osteoblastic and osteocytic differentiation from mesenchymal stem cells (MSC) using mouse MSC line KUSA-A1 and human MSCs. Ninety types of miRNA were quantified during osteoblastic/osteocytic differentiation in KUSA-A1 cells utilizing miRNA PCR arrays. Coincidently with mRNA induction of the osteoblastic and osteocytic markers, the expression levels of several dozen miRNAs including miR-30 family, let-7 family, miR-21, miR-16, miR-155, miR-322 and Snord85 were changed during the differentiation process. These miRNAs were predicted to recognize osteogenic differentiation-, stemness-, epinegetics-, and cell cycle-related mRNAs, and were thus designated OstemiR. Among those OstemiR, the miR-30 family was classified into miR-30b/c and miR-30a/d/e groups on the basis of expression patterns during osteogenesis as well as mature miRNA structures. In silico prediction and subsequent qRT-PCR in stable miR-30d transfectants clarified that context-dependent targeting of miR-30d on known regulators of bone formation including osteopontin/spp1, lifr, ccn2/ctgf, ccn1/cyr61, runx2, sox9 as well as novel key factors including lin28a, hnrnpa3, hspa5/grp78, eed and pcgf5. In addition, knockdown of human OstemiR miR-541 increased Osteopontin/SPP1 expression and calcification in hMSC osteoblastic differentiation, indicating that miR-541 is a negative regulator of osteoblastic differentiation. These observations indicate stage-specific roles of OstemiR especially miR-541 and the miR-30 family on novel targets in osteogenesis.
GEE analysis showed that smoking was a risk factor for early implant failure, and several risk factors were identified for late implant failure.
Biomineralization involves complex processes and interactions between organic and inorganic matters, which are controlled in part by the cells. The objectives of this study were, first, to perform a systematic and ultrastructural investigation of the initial mineral formation during secondary ossification center of mouse femur based on material science and biology viewpoint, and then develop novel biomaterials for mineralization based on the in vivo findings. First, we identified the very initial mineral deposition at postnatal day 5 (P5) at the medial side of femur epiphysis by nanocomputed tomography. Initial minerals were found in the surroundings of hypertrophic chondrocytes. Interestingly, histological and immunohistochemical analyses showed that initial mineralization until P6 was based on chondrocyte activity only, i.e., it occurred in the absence of osteoblasts. Moreover, electron microscopy-based ultrastructural analysis showed that cell-secreted matrix vesicles were absent in the early steps of osteoblast-independent endochondral ossification. Instead, chondrocyte membrane nanofragments were found in the fibrous matrix surrounding the hypertrophic chondrocytes. EDS analysis and electron diffraction study indicated that cell membrane nanofragments were not mineralized material, and could be the nucleation site for the newly formed calcospherites. The phospholipids in the cell membrane nanofragments could be a source of phosphate for subsequent calcium phosphate formation, which initially was amorphous, and later transformed into apatite crystals. Finally, artificial cell nanofragments were synthesized from ATDC5 chondrogenic cells, and in vitro assays showed that these nanofragments could promote mineral formation. Taken together, these results indicated that cell membrane nanofragments were the nucleation site for mineral formation, and could potentially be used as material for manipulation of biomineralization.
Occlusal dysesthesia refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. This systematic review aimed to draw a picture of such patients, to present an agreement of previously reported diagnostic criteria and to analyse the evidence level of the recommended management approaches. An electronic search for all relevant reports on occlusal dysesthesia was thoroughly performed based on previous nomenclatures (e.g. phantom bite, occlusal hyperawareness) in PubMed and The Cochrane Library in July, 2011. A total of 84 reports were matched, among which only 11 studies were included after a two-step (abstract and detailed full-text revision) screening process. Additionally, a thorough manual review of reference lists of the included reports enabled the inclusion of two additional studies. Data analysis revealed that 37 occlusal dysesthesia patients presented a mean age of 51.7 ± 10.6 years and were predominantly women (male/female: 1/5.1) with symptom duration of more than 6 years (average: 6.3 ± 7.5 years) and with concomitant psychological disturbances (e.g. mood disorders, somatoform disorders, personality disorders). Only four authors presented diagnostic criteria for occlusal dysesthesia, which served as the basis for an agreement in the diagnostic criteria. Treatment approaches included psychotherapy, cognitive/behaviour therapy, splint therapy and prescription of anti-depressants or anti-anxiety drugs. Classification of evidence level of management approaches, however, revealed that most of them were expert opinions with single- or multiple-case report(s). Future studies are necessary for a deeper understanding of the mechanisms behind the occlusal dysesthesia symptoms, and consequently, for improvements in evidence-based management approaches.
The results of this pilot study suggest a possible correlation between peripheral platelet serotonin transporter uptake ability and SB severity.
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