Search

Objectives: Mesenchymal stem cells (MSCs) offer a promising therapy in dentistry because of their multipotent properties. Selecting donor MSCs is crucial because Beagle dogs (canines) commonly used in preclinical studies have shown variable outcomes, and it is unclear whether canine MSCs (cMSCs) are skeletal site specific. This study tested whether jaw and long bone cMSCs have disparate in vitro and in vivo multilineage differentiation capabilities.Study Design: Primary cMSCs were isolated from the mandible (M-cMSCs) and femur (F-cMSCs) of four healthy Beagle dogs. The femur served as the non-oral control. Clonogenic and proliferative abilities were assessed. In vitro osteogenic, chondrogenic, adipogenic, and neural multilineage differentiation were correlated with in vivo bone regeneration and potential for clinical applications.Results: M-cMSCs displayed two-fold increase in clonogenic and proliferative capacities relative to F-cMSCs (P = .006). M-cMSCs in vitro osteogenesis based on alkaline phosphatase (P = .04), bone sialoprotein (P = .05), and osteocalcin (P = .03), as well as adipogenesis (P = .007) and chondrogenesis (P = .009), were relatively higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural expression markers, nestin and βIII-tubulin, were not significantly different.Conclusions: The enhanced differentiation and bone regenerative capacity of mandible MSCs may make them favorable donor graft materials for site-specific jaw bone regeneration. [ABSTRACT FROM AUTHOR]

Objectives: Osteoradionecrosis (ORN) is common in the jaws after radiotherapy. We hypothesized that the mandible is more susceptible to ORN than the tibia, based on site disparity in hypoxic, hypocellular, and hypovascular tissue breakdown. Study Design: Twelve rats received 50 Gy irradiation to mandible or tibia; 4 of the rats further received minor surgical trauma to the irradiated sites. Structural and cellular skeletal changes were assessed with computerized tomography, histology, and immunostaining. Results: Mandible developed ORN with 70% mean bone loss 10 weeks after irradiation (P < .05), whereas tibia was structurally and radiologically intact 20 weeks after irradiation. Hypocellularity, hypoxia, and oxidative stress were higher in irradiated mandible (P < .001) than tibia (P < .01) but vascular damage was similar at both skeletal sites. Combined effects of radiation and minor trauma promoted mandibular alveolar bone loss and tibial fracture. Conclusions: ORN has a more rapid onset in mandible than in tibia in the rat. [Copyright &y& Elsevier]

The objective of this systematic review was to evaluate the risk for spontaneous occurrence of medicated-related osteonecrosis of the jaw (MRONJ) in patients with fibrous dysplasia (FD) and McCune-Albright syndrome (MAS). FD is a rare genetic disorder caused by somatic activating mutations of the GNAS locus encoding the Gsα signaling protein, resulting in reduction of GTPase activity and prolonged activation of Gsα, leading to excessive production of Cyclic adenosine monophosphate (cAMP), which disrupts the ability of bone mesenchymal stem cells to differentiate to mature osteogenic cells. With the increased use of bisphosphonates for the antiresorptive properties, the role of antiresorptives in controlling activity within FD lesions and improvement of bone quality is still inconclusive. A systematic review of the literature was performed by searching PubMed and EMBASE databases using controlled search vocabulary, namely, fibrous dysplasia, McCune-Albright syndrome, jaw, osteonecrosis, antiresorptives, antiresorptive therapy, bisphosphonate, denosumab, teriparatide, estrogen, estrogen therapy, hormone therapy, raloxifene, bazedoxifene, calcitonin, and cathepsin K inhibitor. Articles were limited to human studies, in the English language, in which patients were on antiresorptives for at least 2 years. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines were used to eliminate nonrelevant studies. The patient, intervention, comparison, outcome, and time (PICOT) question asked was, "Do antiresorptives cause spontaneous occurrence of MRONJ in patients with FD/MAS monitored for at least 2 years of therapy?" Among the 65 records screened, only 3 articles were eligible for qualitative synthesis based on PRISMA screening criteria. There were no reported cases of spontaneous MRONJ among the patients with FD/MAS across these studies. This is a significant finding among this cohort of patients. Patients with FD demonstrated low susceptibility to spontaneous occurrence of MRONJ, but more confirmatory studies are still needed. This systematic review was limited by the low number of FD/MAS eligible studies. This could be because of the rare genetic nature of FD/MAS, with low patient recruitment in clinical studies among factors. These pose significant challenges to implementing well-designed randomized placebo-controlled clinical trials that focus on antiresorptive-induced osteonecrosis of the jaw in FD/MAS. As more clinical studies become available, a future follow-up systematic review may provide additional insights into MRONJ complications in patients with FD/MAS treated with antiresorptives. [ABSTRACT FROM AUTHOR]

Ameloblastoma is the most clinically significant benign odontogenic tumor of the jaws. Ameloblastomas have a locally aggressive growth pattern and a high rate of malignant transformation. The etiopathogenesis of ameloblastoma is still unknown, and there is still a paucity of information on the factors regulating the locally aggressive growth characteristics of ameloblastoma. Hypoxia and autophagy are 2 mechanistic processes associated with tumor behavior as several tumor cells induce a hypoxic microenvironment to survive. Epithelium-derived ameloblastoma cells (EPAMCs) demonstrate enhanced basal autophagy, but the roles of hypoxia and autophagy in EPAMC survival and ameloblastoma recurrence are still unknown. To understand ameloblastoma pathogenicity and behavior, the goals of this study were to assess differential expression of ameloblastoma-specific and autophagy markers in primary and recurrent ameloblastoma and to assess the roles of hypoxia and autophagy in EPAMC survival. Our hypotheses were that ameloblastoma expresses markers similar to odontogenic epithelial tissue and hypoxia induces oxidative stress and activates autophagy in EPAMCs, favoring their survival and recurrence. Primary and recurrent ameloblastoma tissues from 2 patients were immunostained with pan-cytokeratin, vimentin, and SQSTM1/p62 to assess the expression levels of ameloblastoma and autophagic markers. Additionally, EPAMCs were subjected to severe hypoxia (0.1% O 2) and then allowed to recover for 24 hours in order to define responsiveness to hypoxia based on expression levels of hypoxic (hypoxia-inducible factor [HIF]-1α), survival (phosphorylated extracellular signal-regulated kinase 1/2), and autophagic (Beclin1, phosphorylated 40S ribosomal protein S6 [pS6], SQSTM1/p62, LC3A/B) markers as detected by Western blotting. Previously characterized human odontoma-derived cells (HODCs) served as control odontogenic cells. All experiments were performed in at least triplicates. Data were analyzed as fold change relative to normoxia and expressed as mean ± standard deviation. A paired t test comparison of means was done to compare the expression of autophagy proteins when cells were under normoxia to protein expression under hypoxia and recovery conditions. The Welch 2-sample t test was used to compare fold changes from normoxia in EPAMCs and HODCs with each other. P values were adjusted for multiple comparisons using the Benjamini-Hochberg procedure. Both primary and recurrent tissue samples stained positive for pan-cytokeratin in the cytoplasm of the ameloblastoma islands. Vimentin and SQSTM1/p62 were undetectable in all samples, but the connective tissue stained positive for vimentin. Relative to normoxia, HIF-1α and SQSTM1/p62 expression was increased when the EPAMCs were reoxygenated (P =.056). pS6 levels were decreased in EPAMCs in both hypoxia (P =.005) and recovery (P =.005) compared with basal levels. Hypoxia, however, did not induce any significant changes among the remainder of the hypoxic, survival, and autophagic markers; no statistically significant difference was observed between the EPAMCs and HODCs. The results of this pilot study provide insight into the pathogenicity of ameloblastoma and the possible behavior of EPAMCs when subjected to hypoxia. Our observation of vimentin expression alongside the pan-cytokeratin pattern is consistent with an epithelial origin of both primary and recurrent ameloblastoma. In EPAMCs, canonical autophagy tended to increase with hypoxia and did not recover when cells were reoxygenated, as evident by the increased HIF-1α and SQSTM1/p62 and the reduced levels of pS6 24 hours following hypoxia. This supports EPAMCs re-establishing basal autophagy after severe hypoxia and that recurrence of ameloblastoma may be related to autophagy. [ABSTRACT FROM AUTHOR]

McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain, and compromised oral health. Maxillomandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There are limited data on the outcomes of dental treatments in maxillomandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillomandibular FD within the context of MAS. [ABSTRACT FROM AUTHOR]

McCune–Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain, and compromised oral health. Maxillomandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There are limited data on the outcomes of dental treatments in maxillomandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillomandibular FD within the context of MAS. [ABSTRACT FROM AUTHOR]