Comparison of diagnostic methods for detection of BRAFV600E mutation in ameloblastoma.

BACKGROUND: Ameloblastoma is an aggressively growing, highly recurrent odontogenic jaw tumor. Its association with BRAFV600E mutation is an indication for BRAFV00E-inhibitor therapy The study objective was to identify a sensitive low-cost test for BRAFV600E-positive ameloblastoma. We hypothesized that immunohistochemical staining of formalin-fixed paraffin-embedded tissues for BRAFV600E mutation is a low-cost surrogate for BRAFV600E gene sequencing when laboratory resources are inadequate for molecular testing. METHODS: Tissues from 40 ameloblastoma samples were retrieved from either formalin-fixed paraffin-embedded blocks, RNAlater™ stabilization solution or samples inadvertently pre-fixed in formalin before transfer to RNAlater™. BRAFV600E mutation was assessed by Direct Sanger sequencing, Amplification Refractory Mutation System-PCR and immunohistochemistry (IHC). RESULTS: BRAFV600E mutation was detected by IHC, Amplification Refractory Mutation System-PCR and Direct Sanger sequencing in 93.33%, 52.5% and 30% of samples respectively. Considering Direct Sanger sequencing as standard BRAFV600E detection method, there was significant difference between the three detection methods (𝜒2 (2) = 31.34, p < 0.0001). Sensitivity and specificity of IHC were 0.8 (95% CI: 0.64-0.90) and 0.9 (95% CI: 0.75-0.99) respectively, while positive predictive value and negative predictive value (NPV) were 0.9 and 0.8 (Fischer's test, p < 0.0001) respectively. Sensitivity and specificity of Amplification Refractory Mutation System-PCR detection method were 0.7 (95% CI: 0.53-0.80) and 0.9 (95% CI = 0.67-0.98) respectively, while PPV and NPV were 0.9 and 0.6 respectively (Fischer's test, p < 0.0001). CONCLUSION: Low-cost and less vulnerability of IHC to tissue quality make it a viable surrogate test for BRAFV600E detection in ameloblastoma. Sequential dual IHC and molecular testing for BRAFV600E will reduce equivocal results that could exclude some patients from BRAFV600E-inhibitor therapies.

Application of Panoramic Radiography in the Detection of Osteopenia and Osteoporosis-Current State of the Art.

PURPOSE OF REVIEW: Osteoporosis ranks high among morbidities in the elderly as it is a natural process to lose bone, making them susceptible to fractures from minor falls. The cost of managing these patients is staggering. The fractures can be prevented with better care of the elderly, and by treating the major predisposing factor, osteoporosis. Clinicians and scientists, in general, constantly look for early diagnostic and prognostic indicators for osteopenia and osteoporosis to proactively prevent fractures. Dental panoramic radiography (DPR) is a rotational pantomography used for identifying dental pathology in patients. Early signs of osteopenia and osteoporosis can be identified in DPR. The usefulness of notable jaw changes in DPR to predict osteopenia and osteoporosis is still evolving as more studies continue to delve into this concept. The purpose of this review is to present advances made in the practical application of DPR for predicting early onset of osteopenia and osteoporosis. RECENT FINDINGS: Dental panoramic radiography, a form of tomography commonly used by dental practitioners, has been the standard of care for decades for detecting dento-alveolar pathology. Several technological advancements have taken place with respect to the use of DPR. These include conversion from plain film to digital radiography, advancements in the manufacture of flat panel detectors, and accurate imaging of the layers of mandible and maxilla that has become possible with appropriate patient positioning within the focal trough of the machine. Improvements in the software infrastructure make it easier to view, enhance, and save the radiographic images. The radiographic appearance of the trabecular bone within the mandible and indices measured from the dental panoramic radiographs focusing on the inferior cortex of the mandible are considered useful tools for identifying asymptomatic individuals with osteoporosis or at risk for developing osteoporosis. These indices apparently correlate with risks of fragility fractures of osteoporosis in other parts of the body. Dental panoramic radiography (DPR) is a commonly used radiographic procedure in dentistry for evaluation of teeth and associated maxillofacial structures. The evaluation of the inferior border of the mandible for reduction or loss of cortical thickness and evaluation of the trabecular bone within the mandible are helpful markers for early signs of osteopenia to identify patients at risk for osteoporosis. This review focused on research advancements on practical application of DPR in early identification of osteopenia and osteoporosis.

Oral health outcomes in an HIV cohort with comorbidities- implementation roadmap for a longitudinal prospective observational study.

BACKGROUND: Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. METHODS: We describe here the study design, including processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management and statistical plan. DISCUSSION: We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We also highlight the rigors and challenges associated with our ongoing participant recruitment and retention. A rigorous prospective longitudinal study requires proper planning and execution. A great benefit is that large data sets are collected and biospecimen repository can be used to answer more questions in future studies including genetic, microbiome and metabolome-based studies. TRIAL REGISTRATION: National Institute of Health Clinical Trials Registration (NCT) #: NCT04645693.

Hypoxia enhances basal autophagy of epithelial-derived ameloblastoma cells.

Ameloblastoma is a locally aggressive odontogenic tumor. Etiopathogenesis and locally aggressive growth properties of ameloblastoma can be attributed to a hypoxic microenvironment conducive to tumor cell survival. Epithelial-derived follicular ameloblastoma cells (EP-AMCs) display enhanced basal autophagy, but the interplay of hypoxia and autophagy in EP-AMCs survival and ameloblastoma recurrence is unclear. We evaluated differential expression of autophagic markers in primary and recurrent ameloblastomas and hypothesized that hypoxia-induced autophagy supports EP-AMC survival. Primary and recurrent ameloblastomas were comparatively assessed for expression levels of pan-cytokeratin, Vimentin, and autophagic markers SQSTM1/p62, LC3, and pS6. EP-AMCs compared with human odontoma-derived cells (HODCs) were subjected to severe hypoxia to determine the interplay of hypoxia and autophagic process in posthypoxia survival. Pan-cytokeratin and SQSTM1/p62 were expressed by both primary and recurrent ameloblastoma epithelial cells while the ameloblastoma connective tissues displayed weak reactivity to vimentin. Under hypoxia, EP-AMC expression levels of hypoxia-inducible factor (HIF)-1α, p62, and LC3 were increased while pS6 was decreased posthypoxia. The combined decrease in pS6 and enhanced LC3 in EP-AMCs under hypoxia indicate that EP-AMCs re-establish basal autophagy under hypoxia. Taken together, these suggest a possible role of LC3-associated phagocytosis (LAP) in ameloblastoma cell survival.

Unusual oral multifocal epithelial hyperplasia in an adult African-American lung transplant patient.

Oral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65-year-old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV-related precancerous lesions.

Primary Cilia Enhance Osteogenic Response of Jaw Mesenchymal Stem Cells to Hypoxia and Bisphosphonate.

PURPOSE: Primary cilia play a significant role in mesenchymal stem cell (MSC) lineage commitment, skeletal development, and bone homeostasis. MSC responsiveness to metabolic stress is associated with radiation and drug-induced jaw osteonecrosis. Therefore, we hypothesize that orofacial MSCs (OFMSCs) osteogenic commitment in response to cellular stressors hypoxia and bisphosphonates is a survival response coupled to primary cilia biogenesis. MATERIALS AND METHODS: Human OFMSCs were subjected to cellular stress using severe hypoxia, nitrogen-containing bisphosphonate (pamidronate) and low serum starvation. OFMSC primary cilia formation, as well as cell survival and proliferation, were detected using immunofluorescence, CellTitre-Glo, and WST-1 assays respectively. OFMSC differentiation was tested using Alizarin Red S staining. OFMSCs survival and osteogenic markers were assessed by western blotting relative to primary cilia number and associated acetylated tubulin levels. RESULTS: Baseline OFMSC proliferation was stable under short-term severe hypoxia and pamidronate treatments whether combined with or without serum starvation. Hypoxia and pamidronate decreased the number of OFMSCs positive for primary cilia that was consistent with increased HIF-1α and caspase 3 but decreased cyclin D1. Combined effects of hypoxia and pamidronate on OFMSCs significantly reduced ciliation but did not completely abrogate it. Combination of serum deprivation, hypoxia, and pamidronate promoted OFMSCs osteogenic differentiation that was consistent with upregulated HIF-1α levels. CONCLUSIONS: Partial rather than complete loss of OFMSC ciliation and enhanced osteogenic commitment represent adaptive survival response of OFMSCs to severe hypoxia and pamidronate-induced metabolic stress. Hypoxia and drug-induced OFMSC stress may be significant events governing the pathogenesis and clinical outcomes of jaw osteonecrosis.

Differential Profile of Primary and Recurrent Ameloblastomas Among Afro-descendants and Non-Afro-descendants-a Systematic Review.

Ameloblastoma is an aggressively growing jaw tumor with high recurrent properties. Reports on global and racial distribution of ameloblastoma are variable and inconclusive. The role of race and ethnicity on ameloblastoma growth characteristics, genetic mutational profile, and recurrence is also still unclear. The primary aim of this systematic review was to assess genetic, racial, and ethnic distribution of primary and recurrent ameloblastoma from published literature. The secondary aim was to assess potential correlations between ethnicity, genetic mutation, and disparities in ameloblastoma treatment outcomes in Afro-descendants and non-Afro-descendants. Twenty-three eligible articles were selected based on preferred reporting items for systematic review and meta-analysis (PRISMA), and a total of 169 ameloblastoma cases were evaluated. Data on patient demographics, ameloblastoma growth characteristics, and genetic status were collected for quantitative analysis. Among a total of 169 ameloblastoma cases, Afro-descendant patients had higher primary and recurrent ameloblastomas at 15.5% and 4.7% respectively compared to non-Afro-descendant at 10.7% and 1.8% respectively. Additionally, BRAF V600E was positively associated with 48.8% of all ameloblastomas and strong predilection for Afro-descendants. Despite the paucity of information on genetic profile of ameloblastomas in the Afro-descendant patient cohort, this ethnic group still accounted for 2.95% of all BRAF V600E-positive tumors. These suggest that Afro-descendants are understudied regarding ameloblastoma characteristics, genetic profile, and recurrence profile. Mutational analysis of ameloblastoma tumors in Afro-descendants should be promoted.

Craniofacial disorders and dysplasias: Molecular, clinical, and management perspectives.

There is a wide spectrum of craniofacial bone disorders and dysplasias because embryological development of the craniofacial region is complex. Classification of craniofacial bone disorders and dysplasias is also complex because they exhibit complex clinical, pathological, and molecular heterogeneity. Most craniofacial disorders and dysplasias are rare but they present an array of phenotypes that functionally impact the orofacial complex. Management of craniofacial disorders is a multidisciplinary approach that involves the collaborative efforts of multiple professionals. This review provides an overview of the complexity of craniofacial disorders and dysplasias from molecular, clinical, and management perspectives.

Time to Recurrence of Ameloblastoma and Associated Factors in a Multi-institutional Black Patient Cohort.

Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.

Current concepts in targeted therapies for benign tumors of the jaw - A review of the literature.

The aim of our study was to review current concepts in targeted therapies for benign tumors of the jaw. Benign odontogenic and maxillofacial bone tumors often require radical surgery, with consequent morbidity that impacts patients' postsurgical quality of life. Currently, targeted therapies and novel nonsurgical therapeutics are being explored for management of non-resectable tumors, with the aim of avoiding surgery or minimizing surgical scope. However, data on clinical applications of targeted therapies for benign tumors of the jaw remain sparse. Therefore, a literature review was conducted, based on the PubMed database, which included in vivo human clinical studies describing clinical application of targeted therapy for benign tumor of the jaw. The review assessed the outcomes of BRAF and MEK inhibitors for treatment of ameloblastoma, RANKL monoclonal antibody for treatment of giant cell tumor, cherubism, aneurysmal bone cyst, and fibrous dysplasia, and tyrosine kinase inhibitor for treatment of odontogenic myxoma and cherubism. Targeted therapies decreased tumor size, slowed down tumor progression, and reduced bone pain. Surgery remains the gold standard, but targeted therapies are promising adjuvant or alternative treatment options for reducing tumor progression and morbidity of tumor surgery.

Oral Health Outcomes In An HIV Cohort With Comorbidities- Implementation Roadmap For A Longitudinal Prospective Observational Study.

Long-term antiretroviral therapy (ART) perpetually suppresses HIV load and has dramatically altered the prognosis of HIV infection, such that HIV is now regarded as a chronic disease. Side effects of ART in Patients With HIV (PWH), has introduced new challenges including "metabolic" (systemic) and oral complications. Furthermore, inflammation persists despite great viral load suppression and normal levels of CD4+ cell count. The impact of ART on the spectrum of oral diseases among PWH is often overlooked relative to other systemic complications. There is paucity of data on oral complications associated with ART use in PWH. This is in part due to limited prospective longitudinal studies designed to better understand the range of oral abnormalities observed in PWH on ART. Our group designed and implemented a prospective observational longitudinal study to address this gap. We present a procedural roadmap that could be modelled to assess the extent and progression of oral diseases associated with ART in PWH. We described here the processes associated with subject recruitment and retention, study visit planning, oral health assessments, bio-specimen collection and preprocessing procedures, and data management. We also highlighted the rigors and challenges associated with participant recruitment and retention.

Risks for jaw osteonecrosis drastically increases after 2 years of bisphosphonate therapy.

SUBJECTS: This study consisted of 191 patients older than 40 years with osteonecrosis of the jaw (ONJ) drawn from dental practices in the geographic locations of 3 practice-based research networks (PBRNs). Control patients (n = 573) enrolled were individuals older than 40 years without prior history of ONJ. Three control patients were matched with each ONJ case. The ONJ cases originated from primary, secondary, and tertiary care centers. For each ONJ case diagnosed at a primary care center, the 3 matched controls were selected from the same primary care center. However, controls for cases obtained from secondary or tertiary care centers were selected when possible from the general dental practice that referred the case or from another practice in the same geographic area. KEY RISK/STUDY FACTOR: The key risk factor in this study was bisphosphonate therapy. MAIN OUTCOME MEASURE: The main outcome measure was ONJ. The definition of ONJ was maxillary or mandibular exposed bone of any size that clinically appeared necrotic, without regard for duration or cause. Therefore, all types of jaw osteonecrotic lesions were included in this study; but patients were limited to those diagnosed with onset of ONJ after January 1, 2003, without prior history of facial trauma or sickle cell disease. MAIN RESULTS: The results indicate that 83% of cases and 15% of controls received bisphosphonate therapy for a mean duration (standard error) of 5.6 (0.7) and 4.2 (0.6) years, respectively. Therapy with either intravenous or oral bisphosphonates was highly predictive of ONJ; however, intravenous bisphosphonates (odds ratio [OR] = 299.5; 95% confidence interval [CI] = 70.0- 1282.7) were more associated with ONJ than oral bisphosphonates (OR = 9.8; 95% CI = 5.3- 18.1). Risk of developing ONJ existed within the first 2 years and increased fourfold after 2 years of bisphosphonate use (P < .0001). CONCLUSIONS: The authors concluded that ONJ is causally linked to both intravenous and oral bisphosphonate use, and risk of ONJ escalates tremendously after 2 years of bisphosphonate therapy. The authors also concluded that oral suppuration and dental extractions are independent ONJ risk factors.

Risk of developing spontaneous MRONJ in fibrous dysplasia patients treated with bisphosphonates: a systematic review of the literature.

OBJECTIVE: The objective of this systematic review was to evaluate the risks of medication-related osteonecrosis of the jaw (MRONJ) in fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) patients treated with bisphosphonates. METHOD AND MATERIALS: A systematic review of the literature was performed by searching PubMed and Embase databases using MeSH terms (fibrous dysplasia of bone, "fibrous dysplasia, polyostotic," osteonecrosis, jaw, therapeutics, diphosphonates, denosumab, teriparatide, estrogens, hormones, raloxifene hydrochloride, calcitonin, cathepsin K) and non-MeSH terms (antiresorptive therapy, antiresorptives, bisphosphonate, estrogen therapy, hormone therapy, bazedoxifene, cathepsin K inhibitor). Articles were limited to human studies, in English language, in which patients were on antiresorptives for at least 1 year. PRISMA statement guidelines were used to eliminate non-relevant studies. The PICOT question asked was, "Does exposure to bisphosphonates and other antiresorptives cause occurrence of MRONJ in fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients followed up for at least 1 year?" RESULTS: Eight eligible articles were included in the quantitative synthesis after articles were screened using a PRISMA flowchart. There were 12 reported occurrences of MRONJ among a combined total of 312 fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients (3.85%). CONCLUSION: Patients with fibrous dysplasia or fibrous dysplasia/McCune-Albright syndrome have a low incidence of MRONJ and may apparently have low susceptibility to spontaneous development of MRONJ.

Radiographic Diagnosis of Systemic Diseases Manifested in Jaws.

Radiographic changes of the oral and maxillofacial hard tissues can be an indication of an underlying systemic disease. In this article, the range of individual disease entities that have both systemic and dental manifestations are reviewed. Images for many conditions are provided to illustrate the radiographic changes. A summary of the most common jaw affected, radiographic and pathognomonic findings, and management aspects is listed in a table format within this article for quick reference.

Differentiation and regenerative capacities of human odontoma-derived mesenchymal cells.

Regenerating human tooth ex vivo and biological repair of dental caries are hampered by non-viable odontogenic stem cells that can regenerate different tooth components. Odontoma is a developmental dental anomaly that may contain putative post-natal stem cells with the ability to differentiate and regenerate in vivo new dental structures that may include enamel, dentin, cementum and pulp tissues. We evaluated odontoma tissues from 14 patients and further isolated and characterized human odontoma-derived mesenchymal cells (HODCs) with neural stem cell and hard tissue regenerative properties from a group of complex odontoma tissues from 1 of 14 patients. Complex odontoma was more common (9 of 14) than compound type and females (9 of 14) were more affected than males in our set of patients. HODCs were highly proliferative like dental pulp stem cells (DPSCs) but demonstrated stronger neural immunophenotype than both DPSCs and mandible bone marrow stromal cells (BMSCs) by expressing higher levels of nestin, Sox 2 and betaIII-tubulin. When transplanted with hydroxyapatite/tricalcium phosphate into immunocompromised mice, HODCs differentiated and regenerated calcified hard tissues in vivo that were morphologically and quantitatively comparable to those generated by DPSCs and BMSCs. When transplanted with polycaprolactone (biodegradable carrier), HODCs differentiated to form new predentin on the surface of a dentin platform. Newly formed predentin contained numerous distinct dentinal tubules and an apparent dentin-pulp arrangement. HODCs represent unique odontogenic progenitors that readily commit to formation of dental hard tissues.

Clinical Evaluation and Anatomic Variation of the Oral Cavity.

Clinicians should be knowledgeable about the anatomy of the oral cavity and variations of normal because of oral and systemic health connections. This article presents an overview of normal and variations of normal anatomy of the oral cavity.

Consistency of color-deconvolution for analysis of image intensity of alpha smooth muscle actin-positive myofibroblasts in solid multicystic ameloblastomas.

Ameloblastoma is an odontogenic tumor with a slow, locally aggressive growth pattern and multiple clinico-histologic types. The number of stromal myofibroblasts within ameloblastoma often is correlated with growth and aggressiveness. Color-deconvolution to separate different colors of immunostained tissues is a promising approach to quantifying myofibroblasts in tumors such as ameloblastoma. We investigated the reliability of the color-deconvolution method using cross-sectional design to evaluate alpha-smooth muscle actin (α-SMA)-positive myofibroblasts in solid multicystic ameloblastoma. Formalin fixed tissues of eight cases of solid multicystic ameloblastoma were immunostained for α-SMA using the horseradish peroxidase-diaminobenzidine (HRP-DAB) method. Color-deconvolution using ImageJ software was used to quantify the staining intensity of brown DAB α-SMA stained myofibroblasts. Color-deconvoluted images of brown DAB stained tissues exhibited distinct morphological features of solid multicystic ameloblastoma with α-SMA stained myofibroblasts distributed abundantly adjacent to the ameloblastoma epithelial islands. The computed image intensity of α-SMA stained myofibroblasts was quantitatively similar among the different ameloblastoma samples. A combination of color-deconvolution and α-SMA staining of myofibroblasts is a useful diagnostic tool for evaluating histologic differentiation and growth pattern of ameloblastoma.

Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells.

Are drug-related dental management cautions in Lexicomp Online for Dentistry evidence-based? A systematic review of the literature.

OBJECTIVES: Drug reference databases provide information on potential drug-related medical complications in a dental patient. It is important that database entries and recommendations are supported by evidence-based original studies focused on drug-related dental management complications. The aim of this study was to review and identify database drug categories associated with evidence-based drug-related medical complications during dental treatment. DATA SOURCES: Relevant publications on adverse drug reactions and dental management complications were thoroughly reviewed from the literature published between July 1975 and July 2019. METHOD AND MATERIALS: The drug reference database "Lexicomp Online for Dentistry" was reviewed to identify medications associated with the highest propensity to trigger drug-related dental management complications, and these were correlated with published original studies in PubMed, Embase, and Scopus databases that associated drug actions with dental treatment complications. RESULTS: Fifty-four publications (1.2% of all full-text articles) reported original studies that directly tested drug associations with dental management complications. The cautions in the drug reference database on drug-related dental treatment mainly focused on local anesthetic precaution (P < .001), xerostomia (P < .001), bleeding (P < .001), and a combination of xerostomia and bleeding (P < .001). Antipsychotics/antidepressants were mostly associated with local anesthetic complications (80.95%), xerostomia (81.93%), and a combination of xerostomia and bleeding (22.89%). Bleeding complication was associated with anticoagulants (80.00%) and cancer chemotherapeutic agents (59.21%). CONCLUSIONS: Similarities exist within and across different drug categories in the database entries on drug-related medical complications in a dental patient. There were a relatively limited number of publications that directly tested the association between drug-related medical complications and dental therapies. CLINICAL RELEVANCE: The most common drug cautions during dental treatment reported in Lexicomp Online for Dentistry were limited to drug-drug interactions with local anesthetic actions, excessive bleeding, xerostomia, or a combination of any of these. These recommendations were supported by limited evidence-based studies.

Enhanced basal autophagy supports ameloblastoma-derived cell survival and reactivation.

OBJECTIVES: Ameloblastoma is an aggressive odontogenic jaw neoplasm. Its unlimited growth confers high potential for malignant transformation and recurrence. It is unclear why ameloblastoma is highly recurrent despite surgical resection with a wide margin of normal tissue. While canonical autophagy can be used to degrade and eliminate damaged cellular components, it is also a protective mechanism that provides energy and vital metabolites for cell survival. We used ameloblastoma-derived cells to test the hypothesis that autophagic processes play a role in survival and reactivation of ameloblastoma. METHODS: Primary epithelial (EP-AMCs) and mesenchymal (MS-AMCs) ameloblastoma-derived cells were established from tissue samples of solid multicystic ameloblastoma. Clonogenic capacity and basal autophagic capacity were assessed in ameloblastoma-derived cells relative to human odontoma-derived cells (HODCs) and maxilla-mesenchymal stem cells (MX-MSCs). Ability of ameloblastoma-derived cells to survive and form new ameloblastoma was assessed in mouse tumor xenografts. RESULTS: EP-AMCs were highly clonogenic (p < 0.0001) and demonstrated enhanced basal levels of autophagic proteins microtubule-associated protein 1-light chain 3 (LC3) (p < 0.01), p62 (Sequestosome 1, SQSTM1) (p < 0.01), and the LC3-adapter, melanoregulin (MREG) (p < 0.05) relative to controls. EP-AMCs xenografts regenerated solid ameloblastoma-like tumor with histological features of columnar ameloblast-like cells, loose stellate reticulum-like cells and regions of cystic degeneration characteristic of follicular variant of solid multicystic ameloblastoma. The xenografts also displayed stromal epithelial invaginations strongly reactive to LC3 and p62 suggestive of epithelial-mesenchymal transition and neoplastic odontogenic epithelium. CONCLUSIONS: EP-AMCs exhibit altered autophagic processes that can support survival and recurrence of post-surgical ameloblastoma cells.