Diagnosis and rehabilitation of an infant with palatal mucormycosis: A clinical report and systematic literature review.

STATEMENT OF PROBLEM: Oral mucormycosis is uncommon in pediatric patients with hematolymphoid diseases. Prosthetic rehabilitation is challenging, and protocols are scarce in the literature. PURPOSE: The purpose of this clinical report and systematic literature review of case reports and case series was to describe the clinicopathologic aspects of oral mucormycosis and the interim prosthetic rehabilitation of an affected infant. MATERIAL AND METHODS: The clinical lesions were ulcerative and necrotic with underlying bone exposure that affected the hard palate. The affected area underwent surgical debridement, and histopathologic analysis was performed. A literature search in PubMed/MEDLINE, Embase, Scopus, and Web of Science up to October 2023 was performed. RESULTS: The histopathological features were consistent with mucormycosis. Topical and systemic antifungals were prescribed. Tooth eruption was insufficient, and an acetate plate without clasp retention, but still with adequate retention, was fabricated. Articulatory, masticatory, and swallowing functions were restored, preventing the passage of food and fluids into the oroantral cavities. Twenty-five articles describing 26 patients with oral mucormycosis related to hematolymphoid disorders affecting the pediatric population were identified. None of the authors of these articles provided information about oral rehabilitation. CONCLUSIONS: Early diagnosis and treatment are essential to increasing the chances of survival for infants affected by oral mucormycosis. Custom-made rehabilitation should be provided to restore oral function and improve the patient's general health.

Experience with 808-nm diode laser in the treatment of 47 cases of oral vascular anomalies.

Treatment of oral vascular anomalies (OVA) has focused on minimally invasive techniques rather than radical surgery. We investigated the efficacy and safety of diode laser using the photocoagulation technique in the management of OVA. Forty-seven subjects with OVA were treated with forced dehydration with induced photocoagulation (FDIP) using diode laser (808 nm/4.5 W). This series consisted mostly of male (63.8%) and non-white (63.8%) patients with a mean age of 57.4 years. Varices (91.5%), venous malformations (6.4%), and hemangiomas (2.1%) with a mean size of 7.1 (±4.9) mm were the conditions treated. OVA presented as a nodular lesion (63.8%) involving mainly the lower lip (46.8%). Pulsed laser mode was used as standard and the number of applications varied from one to four sessions, with the majority requiring only one (83%) FDIP session. Kaplan-Meier analysis revealed that complete clinical healing can occur on the 15th day (n=9/29.5%), followed by the 20th (n=6/45.5%), and 30th (n=7/70.5%) days. Postoperative edema was observed in 31 (66%) patients, and recurrence of the lesion occurred in two (4.2%). Based on the data on complete clinical healing, minimal patient discomfort, and satisfactory esthetic results, we can confirm that FDIP by diode laser is a promising candidate for the safe and efficacious treatment of OVA.

Dental caries and developmental defects of enamel in cerebral palsy: A meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the occurrence of dental caries and developmental defects of enamel (DDE) in individuals with and without cerebral palsy (CP). MATERIALS AND METHODS: We conducted searches across five databases and the grey literature. Data were organized using EndNote 20. Reporting followed the MOOSE checklist. A random-effects model meta-analyses were conducted using RStudio, presenting results as mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). The risk of bias of studies was analyzed using the Newcastle-Ottawa Scale, and the certainty of evidence was assessed using GRADE. RESULTS: Among 1336 identified records, 25 studies involving 59,997 participants (mean age: 11.1 years) were included. Data of 12 were pooled into meta-analyses. No significant differences were found between CP and non-CP individuals across indices: DMFT (k = 7) (MD = 0.31; 95% CI [-0.42-1.05]), dmft (k = 4) (MD = 0.31; 95% CI [-0.50-1.14]), DMFS (k = 2) (MD = -0.61; 95% CI [-20.56-19.33]), dmfs (k = 3) (MD = 0.54; 95% CI [-1.09-2.17]), and DDE (k = 3) (OR = 0.80, 95% CI [0.09-7.31]). The certainty of evidence was very low. CONCLUSION: Individuals with CP do not appear to differ significantly from those without CP in terms of dental caries experience and DDE.

Identification of Epstein-Barr virus after topical treatment for oral hairy leukoplakia: A preliminary study.

BACKGROUND: This study evaluated the presence of Epstein-Barr virus type 1 (EBV-1) DNA in patients living with HIV, before and after three different topical therapy protocols for oral hairy leukoplakia (OHL). METHODS: The sample consisted of five patients treated with topical solution of 25% podophyllin resin; six with 25% podophyllin resin plus 5% acyclovir cream; and four with 25% podophyllin resin plus 1% penciclovir cream. DNA was extracted from OHL scrapings and amplified by the PCR using specific primers for EBV-1 (EBNA-1). RESULTS: Clinical healing of OHL lesions was observed across all treatment groups over time. At baseline, EBNA-1 was detected in all OHL lesions. After treatment, OHL samples from three patients treated with 25% podophyllin resin plus 5% acyclovir cream and from one patient treated with 25% podophyllin resin plus 1% penciclovir cream exhibited negative EBNA-1 viral gene encoding. Despite the clinical resolution of OHL, 11 patients (73.3%) showed EBNA-1 positivity immediately after the lesion disappeared. Three patients (20%) treated with podophyllin resin displayed both EBNA-1 positivity and a recurrence of OHL, in contrast to no recurrence in the other two groups. CONCLUSIONS: These findings suggest potential associations between treatment formulations, EBNA-1 persistence, and the recurrence of OHL lesions.

Oral conditions of children with microcephaly associated with congenital Zika syndrome: a cross-sectional study.

The aim of the present study was to compare the oral conditions of children with congenital Zika syndrome (CZS)-associated microcephaly, non-CZS-associated microcephaly, and normotypical children, as well as to characterize their sociodemographic aspects and medical history. A paired cross-sectional study was carried out on 14 children with CZS-associated microcephaly and 24 age-matched controls, in Belo Horizonte, in southeastern Brazil. Children's oral conditions were assessed: dental caries experience (dmft/DMFT indices); developmental defects of enamel (DDE) index; dental anomalies; mucosal changes; lip sealing, and malocclusion (overjet, overbite, and/or posterior crossbite alterations). The quality of oral hygiene was analyzed by the simplified oral hygiene index. The children's mothers also answered a questionnaire about sociodemographic and medical history data. The variables were analyzed descriptively. Female participants were more prevalent (60.5%), and the mean age of the participants was 4.9 years (±1.4) (range: 2-8 years) and 92.1% of their exhibited some oral condition. All participants with CZS-associated microcephaly showed absence of lip sealing and had malocclusion (100.0%). When compared to the other groups, children with CZS had a higher percentage of dental anomalies (35.7%), mucosal changes (71.4%), and unsatisfactory oral hygiene (64.3%). In a sample composed mainly of female participants aged less than 5 years, the prevalence of oral conditions and unsatisfactory oral hygiene was higher in the group with CZS-associated microcephaly, followed by the group with non-CZS-associated microcephaly. Normotypical children had the highest percentage of dental caries experience.

Fungal footprints in oral cancer: unveiling the oral mycobiome.

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer, with a high mortality rate. There is growing evidence supporting a link between oral cancer and the microbiome. The microbiome can impact various aspects of cancer, such as pathogenesis, diagnosis, treatment, and prognosis. While there is existing information on bacteria and its connection to oral cancer, the fungi residing in the oral cavity represent a significant component of the microbiome that remains in its early stages of exploration and understanding. Fungi comprise a minuscule part of the human microbiome called the mycobiome. Mycobiome is ubiquitous in the human body but a weakened immune system offers a leeway space for fungi to showcase its virulence. The role of mycobiome as a colonizer, facilitator, or driver of carcinogenesis is still ambiguous. Reactivating the mycobiome that undergoes collateral damage associated with cancer treatment can be watershed event in cancer research. The coordinated, virulent, non-virulent behavior of the fungi once they reach a critical density must be hacked, considering its diagnostic, prognostic and therapeutic implications in cancer. This review highlights the diversity of the mycobiome and its potential role in oral cancer.

Melanotic Neuroectodermal Tumor of Infancy: A Case Image.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare benign neoplasm that can be mistaken for malignancies due to its unfamiliarity among clinicians and aggressive clinical appearance. We herein contributed by reporting an additional case of MNTI characterized by an extensive extraoral protrusion in a 2-month-old infant. The lesion involved the anterior maxilla, cheek, and infraorbital region, resulting the displacement of the nose to the contralateral side, and measuring approximately 10 cm in size. Surgical resection of the lesion was performed. After a 6-month follow-up, the patient has shown no evidence of recurrence. The rapid growth and aggressive behavior of MNTI emphasize the importance of an early diagnosis and prompt intervention in order to achieve favorable outcomes.

Oral cancer and oral potentially malignant disorders in patients with Fanconi anemia - A systematic review.

The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality.

Kinetics of neutrophil extracellular traps and cytokines in oral mucositis and Candida infection.

OBJECTIVE: This study investigated the concentrations of neutrophil extracellular traps (NET) and salivary cytokines (IL-1ß, IL-6, IL-8/CXCL8, TNF, and TGF-ß1) in patients undergoing chemotherapy and their associations with oral mucositis (OM) and Candida infection. MATERIALS AND METHODS: This prospective longitudinal study performed at a Brazilian service included 60 adults diagnosed with hematolymphoid diseases. Saliva samples were collected on days D0, D3, D10, and D15. Cytokines were analyzed by ELISA and NET formation by identification of the myeloperoxidase-DNA complex. Oral Candida spp. was cultured. RESULTS: OM occurred in 43.3% of patients and oral candidiasis in 20%. However, 66% of individuals had positive cultures for C. albicans. Higher concentrations of IL-6, IL-8/CXCL8, and TNF and lower concentrations of TGF-ß1 were observed in patients with OM. C. albicans infection contributed to the increase in IL-8/CXCL8, TGF-ß1, and TNF. Individuals with OM or with oral candidiasis had significant reductions in NET formation. In contrast, individuals with C. albicans and with concomitant C. albicans and OM exhibited higher NET formation. CONCLUSION: The kinetics of cytokine levels and NET formation in chemotherapy-induced OM appears to be altered by Candida infection, even in the absence of clinical signs of oral candidiasis.

Orofacial Cryptococcosis: A Challenging Clinical Report and a Systematic Analysis of the Literature.

Cryptococcosis is a neglected fungal disease. The scarcity of studies on oral cryptococcosis is certainly due to rarity and/or underreporting of the disease, especially in Brazil. We describe an example of orofacial cryptococcosis affecting a 57-year-old man after heart transplantation, who presented with multiple erythematous ulcers and erosions distributed in the chin, nasal cavity, labial mucosa, hard palate, and buccal vestibule. Computed tomography revealed opacities and micronodules in the lungs. Histopathological features of the oral and pulmonary lesions were compatible with Cryptococcus spp. Amphotericin B and fluconazole were used for treatment during hospitalization and itraconazole for prolonged therapy after hospital discharge. The patient has been under follow up for 6 months without signs of disease. According to a review conducted in PubMed, Web of Science, Scopus, Embase, and LILACS for data analysis of oral cryptococcosis, 26 reports were described in the literature. Predilection for men was observed (85%), with a male:female ratio of 5.5:1. The mean age of the individuals was 49 ± 15.3 years. Oral cryptococcosis mostly presented as an ulcer (n = 17). The palate and tongue were the most affected sites (n = 9 for each). Amphotericin B was the primary therapy utilized in most patients. Seventeen (65%) individuals survived. Knowledge of the clinicodemographic aspects of oral cryptococcosis is important for clinicians in decision making and surveillance.

Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case-control study.

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.

Oral carcinoma in situ in a middle-aged woman with systemic sclerosis: Report of a rare case and literature review.

Systemic sclerosis (SSc) is a rare multisystem rheumatic autoimmune disease involving the skin, connective tissue, and internal organs. Individuals with SSc are at increased risk of cancer. We herein contribute by reporting a case of carcinoma in situ affecting the lower lip and labial mucosa of a 56-year-old Brazilian female patient, which apparently represents the first case reported in Latin America. Surgical resection of the lesion was performed. After a 2-year follow-up, the patient has shown no evidence of recurrence. According to a literature review in PubMed, Web of Science, Scopus, and Embase databases on SSc-related oral and oropharyngeal cancer, 11 cases have been documented hitherto. Reports of oral carcinoma in individuals with SSc are rare. Clinicians should conduct regular examinations of the oral mucosa of these individuals to permit an early diagnosis, as done in the present case.

Influence of anxiety/depression on chemotherapy-induced oral mucositis and related quality of life: A prospective cohort study.

OBJECTIVE: The impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy. METHODS: This is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated. RESULTS: A total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap. CONCLUSION: Anxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life.

Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms.

AIM: We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro. MATERIALS AND METHODS: Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co-localization of myeloperoxidase (MPO)-citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls. RESULTS: The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO-H3Cit-positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters. CONCLUSIONS: The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

Oral conditions of children with microcephaly associated with congenital Zika syndrome: a cross-sectional study

Abstract The aim of the present study was to compare the oral conditions of children with congenital Zika syndrome (CZS)-associated microcephaly, non-CZS-associated microcephaly, and normotypical children, as well as to characterize their sociodemographic aspects and medical history. A paired cross-sectional study was carried out on 14 children with CZS-associated microcephaly and 24 age-matched controls, in Belo Horizonte, in southeastern Brazil. Children's oral conditions were assessed: dental caries experience (dmft/DMFT indices); developmental defects of enamel (DDE) index; dental anomalies; mucosal changes; lip sealing, and malocclusion (overjet, overbite, and/or posterior crossbite alterations). The quality of oral hygiene was analyzed by the simplified oral hygiene index. The children's mothers also answered a questionnaire about sociodemographic and medical history data. The variables were analyzed descriptively. Female participants were more prevalent (60.5%), and the mean age of the participants was 4.9 years (±1.4) (range: 2-8 years) and 92.1% of their exhibited some oral condition. All participants with CZS-associated microcephaly showed absence of lip sealing and had malocclusion (100.0%). When compared to the other groups, children with CZS had a higher percentage of dental anomalies (35.7%), mucosal changes (71.4%), and unsatisfactory oral hygiene (64.3%). In a sample composed mainly of female participants aged less than 5 years, the prevalence of oral conditions and unsatisfactory oral hygiene was higher in the group with CZS-associated microcephaly, followed by the group with non-CZS-associated microcephaly. Normotypical children had the highest percentage of dental caries experience.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Diagnosis and management of exuberant palatal pyogenic granuloma in a systemically compromised patient - Case report.

AIM: To discuss the diagnosis and treatment of an exuberant oral pyogenic granuloma (OPG) in the palatal region in a systemically compromised patient. METHODS AND RESULTS: A 50-year-old woman presented with extensive and painless nodular mass that extended throughout the palatal region, with difficulty speaking, swallowing and spontaneous bleeding for 6 months. Her medical history showed poorly controlled type II diabetes mellitus and hypertension. The intraoral physical examination also revealed poor oral hygiene and periodontal disease. After clinical and radiographic evaluation, the presumptive diagnosis of OPG was made and complete excision of the lesion was performed. Local hemostatic measures were employed to control bleeding. Microscopic evaluation showed a lobulated lesion composed of many blood capillaries confirming the diagnostic hypothesis. CONCLUSIONS: In summary, individuals with severe periodontal disease and systemic disorders may present exacerbated clinical presentations of OPG.

Proposal of a prophylactic photobiomodulation protocol for chemotherapy-induced oral and oropharyngeal mucositis: a randomized clinical trial.

Photobiomodulation therapy (PBMT) is widely used in oncology settings, but lack of assessment standardization is the main barrier to optimization of clinical protocols. This study analyzed three PBMT protocols for preventing oral and oropharyngeal mucositis (OM) in patients undergoing chemotherapy (CT) and/or hematopoietic stem cell transplantation (HSCT). This is a preliminary randomized blind clinical trial. Group 1 received intraoral prophylactic PBMT, Group 2 received intraoral and oropharyngeal PBMT, and Group 3 received intraoral, oropharyngeal, and extraoral PBMT. The applications were from the first day of CT to day + 10. Clinicodemographic data, CT regimens, types of HSCT, hematological exams, occurrence/severity of OM, odynophagia, and OM-related opportunistic infections were assessed. Sixty participants (age range: 18-74 years) were included; 70% of them underwent CT and 30% HSCT. About 43.3% of patients had OM, while odynophagia was reported by 23.3%. Both Groups 1 and 2 revealed better results. Multivariate analysis showed that HSCT directly influenced the occurrence of OM. Individuals who had undergone allogeneic HSCT were 1.93 times more likely to develop OM (p < 0.001). Group 3 exhibited a higher frequency of OM, albeit of lower grades. This group consisted of half the population who had undergone HSCT, had the highest percentage of melphalan use, and had the lowest mean leukocyte count. The three proposed protocols were effective in preventing and reducing OM, with good tolerance and no reported adverse effects. PBMT is a safe and effective approach to OM prophylaxis in adults undergoing CT/HSCT.

Targeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption.

Previous studies have suggested a role of phosphatidylinositol-3-kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic-induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ-deficient mice (PI3Kγ-/- ), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD ) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ-/- , PI3KγKD/KD , and C57BL/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3Kγ-/- mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin-6 (Il-6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa-Β (Rank) in PI3Kγ-/- and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ-/- animals showed reduced p-Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ-/- mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.