Root resorptions induced by genetic disorders: A systematic review.

OBJECTIVES: Root resorption in permanent teeth is a common pathological process that often follows dental trauma or orthodontic treatment. More rarely, root resorption is a feature of genetic disorders and can help with diagnosis. Thus, the present review aims to determine which genetic disorders could induce pathological root resorptions and thus which mutated genes could be associated with them. METHODS: We conducted a systematic review following the PRISMA guidelines. Articles describing root resorptions in patients with genetic disorders were included from PubMed, Embase, Web of Science, and Google Scholar. We synthesized the genetic disorder, the type, severity, and extent of the resorptions, as well as the other systemic and oral symptoms and histological features. RESULTS: The synthetic analysis included 25 studies among 937 identified records. We analyzed 21 case reports, three case series, and one cohort study. Overall, we highlighted 14 different pathologies with described root resorptions. Depending on the pathology, the sites of resorption, their extent, and their severity showed differences. CONCLUSION: With 14 genetic pathologies suspected to induce root resorptions, our findings are significant and enrich a previous classification. Among them, three metabolic disorders, three calcium-phosphorus metabolism disorders, and osteolysis disorders were identified.

[Oral mesenchymal cells, a specific niche, from development to regeneration]. / Les cellules mésenchymateuses orales, une niche spécifique, du développement à la régénération.

Oral buccal tissues, including bone and mucosa, have unique properties. Oral mucosal fibroblasts and jaw osteoblasts, both derived from Cranial Neural Crest cells, play a key role in healing and repair. These cells express a specific repertoire of genes with their regenerative properties, but also craniofacial diseases. Understanding these tissues holds clinical promise for tissue regeneration and repair of bone and mucosal defects. These multidisciplinary advances also offer potential for better management of periodontal-related conditions and improved oral health.

Title: Les cellules mésenchymateuses orales, une niche spécifique, du développement à la régénération. Abstract: Les tissus muqueux et osseux oraux présentent des propriétés uniques. Les fibroblastes de la muqueuse orale et les ostéoblastes des mâchoires, issus des crêtes neurales crâniennes, jouent un rôle clé dans la cicatrisation/réparation. Ces cellules expriment un répertoire spécifique de gènes associés à leurs propriétés régénératives, mais aussi liés aux maladies rares crâniofaciales. La connaissance de ces tissus ouvre des perspectives cliniques pour la régénération tissulaire et la réparation des défauts osseux et muqueux. Ces avancées multidisciplinaires ont aussi un impact prometteur sur la prise en charge des maladies liées au parodonte et sur l'amélioration de la santé bucco-dentaire.

Oral Health in Patients with History of Head and Neck Cancer: Complexity and Benefits of a Targeted Oral Healthcare Pathway.

PURPOSE OF REVIEW: This work consists in a literature review on the current state of knowledge regarding the oral management of patients with a history of head and neck cancer (HNC), corroborated by clinical cases and illustrated by clear infographic summaries. It aims to provide healthcare professionals with a comprehensive overview of the oral health status of HCN patients. RECENT FINDINGS: Head and neck cancers (HNCs) represent the seventh most common type of cancer worldwide, with over 660,000 annual new cases. Despite the significant negative impact of HNCs on oral health, patients often receive no or inappropriate oral care while the significant impact of oral pathologies on cancer prognosis is commonly underestimated. This work (i) describes the oral cavity during and after HNC through the prism of care complexity and (ii) highlights several potential key factors that could worsen long-time patients' prognosis and quality of life. By investigating the biological, microbiological, functional, and psychological dimensions of the interrelationships between HNCs and oral health, the authors explored the barriers and benefits of a targeted oral healthcare pathway. This article emphasizes the importance of multidisciplinary care and highlights the need for further research elucidating the intricate relationships between oral health and HNCs, particularly through the microbiota.

Role of periosteum during healing of alveolar critical size bone defects in the mandible: a pilot study.

OBJECTIVES: Minipigs present advantages for studying oral bone regeneration; however, standardized critical size defects (CSD) for alveolar bone have not been validated yet. The objectives of this study are to develop a CSD in the mandibular alveolar bone in Aachen minipigs and to further investigate the specific role of periosteum. MATERIALS AND METHODS: Three female Aachen minipigs aged 17, 24, and 84 months were used. For each minipig, a split-mouth design was performed: an osteotomy (2 cm height × 2.5 cm length) was performed; the periosteum was preserved on the left side and removed on the right side. Macroscopic, cone beam computed tomography (CBCT), microcomputed tomography (µCT), and histological analyses were performed to evaluate the bone defects and bone healing. RESULTS: In both groups, spontaneous healing was insufficient to restore initial bone volume. The macroscopic pictures and the CBCT results showed a larger bone defect without periosteum. µCT results revealed that BMD, BV/TV, and Tb.Th were significantly lower without periosteum. The histological analyses showed (i) an increased osteoid apposition in the crestal area when periosteum was removed and (ii) an ossification process in the mandibular canal area in response to the surgical that seemed to increase when periosteum was removed. CONCLUSIONS: A robust model of CSD model was developed in the alveolar bone of minipigs that mimics human mandibular bone defects. This model allows to further investigate the bone healing process and potential factors impacting healing such as periosteum. CLINICAL RELEVANCE: This model may be relevant for testing different bone reconstruction strategies for preclinical investigations.

Orofacial intramuscular lymphoma: first presentation.

The term lymphoma includes a wide variety of different clinical entities including diffuse large B-cell lymphomas (DLBCL). Skeletal muscle or intramuscular lymphomas represent less than 2% of B-cell Lymphoma, they are quite rare, even more in the orofacial area. We present the case of a painless growing mass of the right cheek mimicking a chronic oral cellulitis in a 34-year-old man. Magnetic resonance imaging (MRI) of the mandible revealed a well-defined 7x3cm mass around the core of the mandible that invades the buccal floor and the subcutaneous planes. A whole-body 18F-FDG PET/CT for the initial diagnosis revealed an intensely isolated hypermetabolic band corresponding to a voluminous tumoral permeation. The diagnosis of a skeletal muscle diffuse large B-cell lymphoma was established after an intraoral biopsy. It was treated with 4 chemotherapy cures and showed complete remission at one year of follow-up. This atypical form of lymphoma should be integrated into the differential diagnosis of soft tissue tumors in the oral cavity.

Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization.

Background: Extracellular matrix (ECM) plays a pivotal role in many physiological processes. ECM macromolecules and associated factors differ according to tissues, impact cell differentiation, and tissue homeostasis. Dental pulp ECM may differ from other oral tissues and impact mineralization. Thus, the present study aimed to identify the matrisome of ECM proteins derived from human dental pulp stem cells (DPSCs) and its ability to regulate mineralization even in cells which do not respond to assaults by mineralization, the human gingival fibroblasts (GF). Methods: ECM were extracted from DPSCs cultured in normal growth medium supplemented with L-ascorbic acid (N-ECM) or in osteogenic induction medium (OM-ECM). ECM decellularization (dECM) was performed using 0.5% triton X-100 in 20 mM ammonium hydroxide after 21 days. Mass spectrometry and proteomic analysis identified and quantified matrisome proteins. Results: The dECM contained ECM proteins but lacked cellular components and mineralization. Interestingly, collagens (COL6A1, COL6A2, and COL6A3) and elastic fibers (FBN1, FBLN2, FN1, and HSPG2) were significantly represented in N-ECM, while annexins (ANXA1, ANXA4, ANXA5, ANXA6, ANXA7, and ANXA11) were significantly overdetected in OM-ECM. GF were reseeded on N-dECM and OM-dECM and cultured in normal or osteogenic medium. GF were able to attach and proliferate on N-dECM and OM-dECM. Both dECM enhanced mineralization of GF at day 14 compared to tissue culture plate (TCP). In addition, OM-dECM promoted higher mineralization of GF than N-dECM although cultured in growth medium. Conclusions: ECM derived from DPSCs proved to be osteoinductive, and this knowledge supported cell-derived ECM can be further utilized for tissue engineering of mineralized tissues.

Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders.

Dental anomalies occur frequently in a number of genetic disorders and act as major signs in diagnosing these disorders. We present definitions of the most common dental signs and propose a classification usable as a diagnostic tool by dentists, clinical geneticists, and other health care providers. The definitions are part of the series Elements of Morphology and have been established after careful discussions within an international group of experienced dentists and geneticists. The classification system was elaborated in the French collaborative network "TÊTECOU" and the affiliated O-Rares reference/competence centers. The classification includes isolated and syndromic disorders with oral and dental anomalies, to which causative genes and main extraoral signs and symptoms are added. A systematic literature analysis yielded 408 entities of which a causal gene has been identified in 79%. We classified dental disorders in eight groups: dental agenesis, supernumerary teeth, dental size and/or shape, enamel, dentin, dental eruption, periodontal and gingival, and tumor-like anomalies. We aim the classification to act as a shared reference for clinical and epidemiological studies. We welcome critical evaluations of the definitions and classification and will regularly update the classification for newly recognized conditions.

Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair.

A large array of therapeutic procedures is available to treat cartilage disorders caused by trauma or inflammatory disease. Most are invasive and may result in treatment failure or development of osteoarthritis due to extensive cartilage damage from repeated surgery. Despite encouraging results of early cell therapy trials that used chondrocytes collected during arthroscopic surgery, these approaches have serious disadvantages, including morbidity associated with cell harvesting and low predictive clinical outcomes. To overcome these limitations, adult stem cells derived from bone marrow and subsequently from other tissues are now considered as preferred sources of cells for cartilage regeneration. Moreover, with new evidence showing that the choice of cell source is one of the most important factors for successful cell therapy, there is growing interest in neural crest-derived cells in both the research and clinical communities. Neural crest-derived cells such as nasal chondrocytes and oral stem cells that exhibit chondrocyte-like properties seem particularly promising in cartilage repair. Here, we review the types of cells currently available for cartilage cell therapy, including articular chondrocytes and various mesenchymal stem cells, and then highlight recent developments in the use of neural crest-derived chondrocytes and oral stem cells for repair of cartilage lesions.

Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex vivo treatment.

Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). To date, no non-surgical therapy has been proposed to slow or stop AA progression. Previously published preclinical studies from our team using an aneurysm rabbit model showed a promising concept for treatment of AAs with gingival fibroblast (GFs) which are readily available cells. In this study, we investigated the possible tissue repair of human AAAs and TAAs using ex vivo models co-cultured with GFs. Histological analysis showed that TAA and AAA are two distinct pathologies. Both lesions presented destruction of the aorta wall, highly evidenced in AAA samples. The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. The co-culture of GFs with AA lesions shows increased expression of TIMP-1, the inhibitor of the aneurysm severity marker MMP-9. Our study indicates that GFs might ameliorate aorta wall reestablishment in both AA types by their regenerative and immunomodulatory capacities. It also demonstrates the possible infectious cause of AAA compared with TAA that may explain their different behavior.

Formation of cartilage and synovial tissue by human gingival stem cells.

Human gingival stem cells (HGSCs) can be easily isolated and manipulated in culture to investigate their multipotency. Osteogenic differentiation of bone-marrow-derived mesenchymal stem/stromal cells has been well documented. HGSCs derive from neural crests, however, and their differentiation capacity has not been fully established. The aim of the present report was to investigate whether HGSCs can be induced to differentiate to osteoblasts and chondrocytes. HGSCs were cultured either in a classical monolayer culture or in three-dimensional floating micromass pellet cultures in specific differentiation media. HGSC differentiation to osteogenic and chondrogenic lineages was determined by protein and gene expression analyses, and also by specific staining of cells and tissue pellets. HGSCs cultured in osteogenic differentiation medium showed induction of Runx2, alkaline phosphatase (ALPL), and osterix expression, and subsequently formed mineralized nodules consistent with osteogenic differentiation. Interestingly, HGSC micromass cultures maintained in chondrogenic differentiation medium showed SOX9-dependent differentiation to both chondrocyte and synoviocyte lineages. Chondrocytes at different stages of differentiation were identified by gene expression profiles and by histochemical and immunohistochemical staining. In 3-week-old cultures, peripheral cells in the micromass cultures organized in layers of cuboidal cells with villous structures facing the medium. These cells were strongly positive for cadherin-11, a marker of synoviocytes. In summary, the findings indicate that HGSCs have the capacity to differentiate to osteogenic, chondrogenic, and synoviocyte lineages. Therefore, HGSCs could serve as an alternative source for stem cell therapies in regenerative medicine for patients with cartilage and joint destructions, such as observed in rheumatoid arthritis.

Oral phenotype and scoring of vascular Ehlers-Danlos syndrome: a case-control study.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic condition related to mutations in the COL3A1 gene, responsible of vascular, digestive and uterine accidents. Difficulty of clinical diagnosis has led to the design of diagnostic criteria, summarised in the Villefranche classification. The goal was to assess oral features of vEDS. Gingival recession is the only oral sign recognised as a minor diagnostic criterion. The authors aimed to check this assumption since bibliographical search related to gingival recession in vEDS proved scarce. DESIGN: Prospective case-control study. SETTING: Dental surgery department in a French tertiary hospital. PARTICIPANTS: 17 consecutive patients with genetically proven vEDS, aged 19-55 years, were compared with 46 age- and sex-matched controls. OBSERVATIONS: Complete oral examination (clinical and radiological) with standardised assessment of periodontal structure, temporomandibular joint function and dental characteristics were performed. COL3A1 mutations were identified by direct sequencing of genomic or complementary DNA. RESULTS: Prevalence of gingival recession was low among patients with vEDS, as for periodontitis. Conversely, patients showed marked gingival fragility, temporomandibular disorders, dentin formation defects, molar root fusion and increased root length. After logistic regression, three variables remained significantly associated to vEDS. These variables were integrated in a diagnostic oral score with 87.5% and 97% sensitivity and specificity, respectively. CONCLUSIONS: Gingival recession is an inappropriate diagnostic criterion for vEDS. Several new specific oral signs of the disease were identified, whose combination may be of greater value in diagnosing vEDS.

Phenotypic study of human gingival fibroblasts in a medium enriched with platelet lysate.

BACKGROUND: The modulation abilities of gingival fibroblasts open new therapeutic strategies for the treatment of vascular diseases (e.g., aneurism) and irradiation burns. Culture media are classically supplemented with animal sera to provide nutriments. Unfortunately, because of their potential for interspecies transmission of microorganisms, these media are not used for cells destined for human transplantation. This preliminary phenotypic study aims to test a serum-free (SF) culture medium for human gingival fibroblasts (hGF) supplemented with human platelet lysates (PLs) for rapid cell expansion. METHODS: An SF medium was first elaborated to compete with hGF proliferation in a reference medium containing 10% fetal bovine serum (BSmedium). Adhesion, proliferation, and doubling kinetics were run in the presence of PLs (SF+PL). Cytoskeletal proteins were analyzed and chromosomal abnormalities were evaluated by karyotype analyses. The SF+PL influence on secretion of molecules implied in tissue remodeling (i.e., matrix metalloproteinases [MMPs], their tissue inhibitors [TIMPs], and several growth factors) was studied. RESULTS: SF+PL increased the proliferation rate 1.5-fold in a week compared to BSmedium. Cytoskeleton protein expression was similar in BSmedium and in SF+PL. Chromosomal abnormalities were rare in SF+PL. MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, and the growth factors interleukin-1ß and -4 and transforming growth factor-ß1 secretions were stable during the experiment. TIMP-2 and interleukin-6 were slightly decreased in SF+PL compared to BSmedium. CONCLUSION: While waiting confirmation from a proteomic approach, this SF culture medium could allow a secured faster hGF proliferation adapted for human cell transplant therapy.

Multipotent progenitor cells in gingival connective tissue.

The gum has an exceptional capacity for healing. To examine the basis for this property and explore the potential of conferring it to organs with inferior healing capacity, we sought the presence of progenitor cells in gingival connective tissue. Colony-forming units of fibroblast-enriched cells from gingival fibroblast cultures were assessed for expression of membrane markers of mesenchymal stem cells; capacity to differentiate into osteoblasts, chondroblasts, and adipocytes; and engraftment efficiency after in vivo transfer. On the basis of their ability to differentiate into several lineages, proliferate from single cells, induce calcium deposits, and secrete collagen in vivo after transfer on hydroxyapatite carriers, we suggest that this population represents gingival multipotent progenitor cells. The discovery of progenitor cells in gingival connective tissue may help improve our understanding of how the wounded gum is capable of almost perfect healing and opens the prospect of cellular therapy for wound healing using readily available cells at limited risk to the patient.

Gene expression analysis of troglitazone reveals its impact on multiple pathways in cell culture: a case for in vitro platforms combined with gene expression analysis for early (idiosyncratic) toxicity screening.

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione family are used for the treatment of type 2 diabetes mellitus due to their ability to reduce glucose and lipid levels in patients with this disease. Three thiazolidinediones that were approved for treatment are Rezulin (troglitazone), Avandia (rosiglitazone), and Actos (pioglitazone). Troglitazone was withdrawn from the market due to idiosyncratic drug toxicity. Rosiglitazone and pioglitazone are still on the market for the treatment of type 2 diabetes. The authors present data from a gene expression screen that compares the impact these three compounds have in rats, in rat hepatocytes, and in the clone 9 rat liver cell line. The authors monitored the changes in expression in multiple genes, including those related to xenobiotic metabolism, proliferation, DNA damage, oxidative stress, apoptosis, and inflammation. Compared to the other two compounds, troglitazone had a significant impact on many of the pathways monitored in vitro although no major perturbation was detected in vivo. The changes detected predict not only general toxicity but potential mechanisms of toxicity. Based on gene expression analysis, the authors propose there is not just one but multiple ways troglitazone could be toxic, depending on a patient's environment and genetic makeup, including immune response-related toxicity.