Rogério Bentes Kato

Nanotopography directs mesenchymal stem cells to osteoblast lineage through regulation of microRNA-SMAD-BMP-2 circuit.

The aim of this study was to investigate if chemically produced nanotopography on titanium (Ti) surface induces osteoblast differentiation of cultured human bone marrow mesenchymal stem cells (hMSCs) by regulating the expression of microRNAs (miRs). It was demonstrated that Ti with nanotopography induces osteoblast differentiation of hMSCs as evidenced by upregulation of osteoblast specific markers compared with untreated (control) Ti at day 4. At this time‐point, miR‐sequencing analysis revealed that 20 miRs were upregulated (>twofold) while 20 miRs were downregulated (>threefold) in hMSCs grown on Ti with nanotopography compared with control Ti. Three miRs, namely miR‐4448, ‐4708, and ‐4773, which were significantly downregulated (>fivefold) by Ti with nanotopography affect osteoblast differentiation of hMSCs. These miRs directly target SMAD1 and SMAD4, both key transducers of the bone morphogenetic protein 2 (BMP‐2) osteogenic signal, which were upregulated by Ti with nanotopography. Overexpression of miR‐4448, ‐4708, and 4773 in MC3T3‐E1 pre‐osteoblasts noticeably inhibited gene and protein expression of SMAD1 and SMAD4 and therefore repressed the gene expression of key bone markers. Additionally, it was observed that the treatment with BMP‐2 displayed a higher osteogenic effect on MC3T3‐E1 cells grown on Ti with nanotopography compared with control Ti, suggesting that the BMP‐2 signaling pathway was more effective on this surface. Taken together, these results indicate that a complex regulatory network involving a miR‐SMAD‐BMP‐2 circuit governs the osteoblast differentiation induced by Ti with nanotopography. J. Cell. Physiol. 229: 1690–1696, 2014.

Nanotopography drives stem cell fate toward osteoblast differentiation through α1β1 integrin signaling pathway.

The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2SO4/H2O2 to yield nanotopography and rat MSCs were cultured under osteogenic and non‐osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both osteogenic and non‐osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non‐osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface‐mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration. J. Cell. Biochem. 115: 540–548, 2014.

Removal of a maxillary third molar accidentally displaced into the infratemporal fossa via intraoral approach under local anesthesia: report of a case.

The surgical removal of impacted maxillary third molars is a procedure routinely carried out by dentists and oral surgeons, and it is usually associated with low rates of complications and morbidity. 1,2 These complications frequently include fracture of the tuberosity, tooth root fracture, perforation of the maxillary sinus, prolapse of the buccal fat pad, and displacement of the roots or tooth into the maxillary sinus, all of which may be easily managed. 2,3 Although the displacement of an entire tooth into the infratemporal fossa was once considered a rare complication, 3 it has been reported more frequently in the literature in the last 4 decades. 1,2,4-11 This case report describes the location and surgical removal of a left maxillary third molar displaced into the infratemporal fossa during an unsuccessful surgical removal by the patients dental clinician. The diagnostic and treatment problems and the causes of this complication are also discussed.

Mandibular bisphosphonate-related osteonecrosis after dental implant rehabilitation: a case report.

It has been a matter of debate as to whether dental implant therapies are suitable for patients subjected to long-term use of bisphosphonates (BPs). This report presents a case of a 76-year-old woman who developed BPs-related osteonecrosis of the jaw (BRONJ) in the left hemimandible after dental implant exposure. The implants and the necrotic crestal bone were removed, and postoperatively, a delay in tissue healing with bone exposure was noticed. The histologic analysis of the block biopsies revealed a lamellar bone tissue exhibiting necrotic areas and bacterial colonies associated with the bone outer surface. The bone-implant interface showed viable lamellar bone with enlarged vascular spaces in the areas between the implant threads. The possible mechanisms for the loss of implants in BRONJ patients are discussed, and the potential protocols for dental implant rehabilitation for patients under BP therapies are presented.

Focal osteoporotic bone marrow defect mimicking a mandibular cystic lesion.

An unusual presentation of a focal osteoporotic bone marrow defect (FOBMD) of the mandible mimicking a cystic lesion is documented. A definitive diagnosis could be established only on the basis of the histopathologic evaluation. A 66-year-old Brazilian woman was referred by her dentist for well-defined radiolucency of the mandibular molar region suggesting a cystic lesion of odontogenic origin. The computed tomography scan confirmed that the lesion did not affect the corticals. The biopsy confirmed the diagnosis of FOBMD. The diagnostic difficulty in the current case is obvious, because FOBMD, usually exhibiting an ill-defined radiolucency, is seldom suspected preoperatively when a differential diagnosis is considered for focal well-defined radiolucent areas in the jaws.

Comparative study of bone repair in mandibular body osteotomy between metallic and absorbable 2.0 mm internal fixation systems. Histological and histometric analysis in dogs: a pilot study

The objective of this study was to compare the bone repair along a mandibular body osteotomy stabilized with 2.0 mm absorbable and metallic systems. 12 male, adult mongrel dogs were divided into two groups (metallic and absorbable) and subjected to unilateral osteotomy between the mandibular third and fourth premolars, which was stabilized by applying two 4-hole plates. At 2 and 18 weeks, three dogs from each group were killed and the osteotomy sites were removed and divided equally into three parts: the upper part was labelled the tension third (TT), the lower part the compression third (CT), and the part between the TT and CT the intermediary third (IT). Regardless of the treatment system, union between the fragments was observed at 18 weeks and the CT showed more advanced stages of bone repair than the TT. Histometric analysis did not reveal any significant differences among the 3 parts or systems in the distance between bone fragments at 2 weeks. Although at 18 weeks the proportions of newly formed bone did not differ among TT, IT and CT, significantly enhanced bone formation was observed in all sections for the metallic group. The patterns of repair were distinct between treatments.

Histologic and Histometric Analysis of Bone Repair at the Site of Mandibular Body Osteotomy and at the Bone-Screw Interface After Using a Biodegradable 2.0-mm Internal Fixation System.

AbstractThe aim of the study was to evaluate histologically and histometrically the bone repair at the mandibular body osteotomy and at the bone-screw interface after using a biodegradable 2.0-mm internal fixation system. Six dogs were subjected to an osteotomy in the mandibular body, which was stabilized by applying a fixation device manufactured with poly-L-DL-lactic acid (70:30). The dogs were euthanized at 2 and 18 weeks. Each screw was sectioned along its long axis, and the osteotomy sites were divided into 3 parts: the upper part was labeled the tension third (TT); the lower part, compression third (CT); and the part between the TT and CT, intermediary third (IT). Histologic analysis showed areas of direct contact between the screw surface and the parent lamellar bone at 2 weeks. At 18 weeks, 3 microscopically distinct layers at the bone-screw interface were noted. At the osteotomy sites, union between the bone fragments was observed at 18 weeks. Statistically significant differences in the newly formed bone among TT, IT, and CT (P = 0.019) were observed. In conclusion, the biomechanical environment created by the biodegradable IF system used in this study facilitated bone repair at the osteotomy site.