Vitamin D Deficiency, Chronic Kidney Disease and Periodontitis.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in the host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD) are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D, in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiological mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Modified Tunnel Procedure to Facilitate Ridge Reconstruction of an Extraction Socket Associated with Buccal Dehiscence and Gingival Recession: A Case Report with a 6-year Follow-Up.

Introduction: Extraction sockets associated with buccal dehiscences and gingival recessions pose particular surgical and restorative challenges. In these cases, unassisted healing following flapless tooth extraction results in severe bone and soft tissue deformities and an aesthetic compromise. Root coverage procedures prior to ridge reconstruction may enable predictable alveolar augmentation. Case Presentation. This is the first case report describing the utilisation of modified tunnel procedure to facilitate ridge reconstruction consisting of ovate pontic and xenograft, of tooth #25 in a 38-year-old-male. The 6 months and 1-year reviews showed optimal soft tissue aesthetics, 100% root coverage of the tooth #25, and bone augmentation, which enabled placement of 10.0 mm × 4.0 mm (3i) implant in a prosthetically driven position. The 6-year review continued to show favourable clinical outcomes. Conclusion: Compromised extraction sockets containing buccal dehiscence and associated with gingival recessions may benefit from soft tissue augmentation procedures to enhance the clinical outcome of ridge reconstruction.

The role of vitamin D in periodontal health and disease.

Vitamin D plays an essential role in calcium and bone metabolism, immune regulation and possesses profound anti-inflammatory effects. Evidence suggests that low serum vitamin D is associated with increased severity of periodontitis, a chronic inflammatory condition characterised by destruction of the supporting tissues surrounding the tooth, which has several shared risk factors with other chronic non-communicable diseases. The biological functions of vitamin D are mediated by its strong anti-microbial, anti-inflammatory, and host modulatory properties. Experimental periodontitis models involving targeted deletion of 1α-hydroxylase, the enzyme responsible for the conversion of inactive substrate to active 1,25(OH)2 D3 (calcitriol), showed augmented alveolar bone loss and gingival inflammation. Vitamin D receptor (VDR) gene polymorphisms have also been associated with increased severity of periodontitis. Thus, the involvement of vitamin D in the pathogenesis of periodontitis is biological plausible. Clinical studies have consistently demonstrated an inverse relationship between serum 25OHD3 and periodontal disease inflammation. However, due to the paucity of well-designed longitudinal studies, there is less support for the impact of vitamin D status on periodontal disease progression and tooth loss. The evidence emphasises the importance of maintaining vitamin D sufficiency in supporting periodontal health. This review aims to first examine the biological mechanisms by which vitamin D might influence the pathogenesis of periodontal disease and second, discuss the clinical evidence which implicate the role of vitamin D in periodontal disease.

Development of an in vitro model of the dentogingival junction using 3D organotypic constructs.

OBJECTIVES: The overall aim was to propose a plausible model of the dentogingival junction (DGJ) to deepen our understanding of the extrinsic influences responsible for the development of the junctional epithelial phenotype. The specific objective was to test the hypothesis that epithelial migration and proliferation would be inhibited by periodontal ligament (PDL) fibroblasts in an in vitro model of the DGJ consisting of 3D organotypic cultures. BACKGROUND: Previously, we showed that 3D organotypic cultures containing human gingival fibroblasts (HGF) supported the development of a multi-layered epithelium, while constructs containing human periodontal ligament fibroblasts (HPDLF) resulted in epithelial atrophy (Lu EMC, Hobbs C, Dyer CJ, Ghuman M, Hughes FJ. J Perio Res., 2020). However, changes in epithelial phenotype have not been studied within an in vitro model of the DGJ. METHODS: The in vitro model of the DGJ comprised of a donor HGF construct (H400 epithelium overlying HGF-collagen matrix) supported by a dimensionally larger recipient collagen bed enriched with HPDLF. Samples were harvested, fixed and processed for immunohistochemistry. The changes in epithelial migration and proliferation following contact with HPDLF were assessed by measuring the horizontal extension of the epithelial outgrowth on the recipient collagen matrix. RESULTS: Within our in vitro model of the DGJ, epithelial migration and proliferation were inhibited following contact with the recipient HPDLF. By contrast, the control set-up showed a relative increase in epithelial growth, where the epithelium came into contact with the recipient HGF. Overall, there were limited changes in the molecular expression of keratin markers. CONCLUSION: This study has proposed a plausible in vitro model of the DGJ to illustrate the role of different fibroblasts in the regulation of dentogingival epithelia. Furthermore, it suggests that the anatomical positional stability of the JE and its apparent resistance to apical migration could be associated with its interaction with the PDL.

Differential regulation of epithelial growth by gingival and periodontal fibroblasts in vitro.

OBJECTIVES: To investigate the underlying molecular mechanisms by which gingival and periodontal ligament (PDL) fibroblasts regulate epithelial phenotype. BACKGROUND: Fibroblast populations regulate the epithelial phenotype through epithelial-mesenchymal interactions (EMI). Previous studies have proposed that maintenance of the junctional epithelium (JE) is dependent on the differential effects from gingival and PDL tissues. However, these cell populations are undefined and the signalling mechanisms which may regulate JE are unknown. METHODS: Immunohistochemical analyses were performed on formalin-fixed paraffin-embedded sections of dentogingival tissues to identify phenotypic differences in fibroblast populations. The effect of distinct fibroblasts on epithelial phenotype was studied via 3D organotypic cultures, consisting of an H400 epithelium supported by human gingival fibroblasts (HGF) or human periodontal ligament fibroblasts (HPDLF), embedded in collagen gel. To investigate the involvement of Wnt signalling in EMI, the Wnt antagonist rhDKK1 was added to HGF constructs. The gene expression of Wnt antagonists and agonists was tested via RNA extraction and qPCR. Specific gene silencing using RNA interference was performed on HPDLF/HGF constructs. RESULTS: Gingival fibroblasts were characterized by Sca1 expression, and PDL fibroblasts, characterized by Periostin and Asporin expression. Through the construction of 3D organotypic cultures, we showed that HGF supported epithelial multilayering, whilst HPDLF failed to support epithelial cell growth. Furthermore, HGF constructs treated with rhDKK1 resulted in a profound reduction in epithelial thickness. We identified SFRP4 to be highly specifically expressed in HPDLF, at both the mRNA and protein levels. A knockdown of SFRP4 in HPDLF constructs led to an increase in epithelial growth. CONCLUSION: The study demonstrates the presence of phenotypically distinct fibroblast populations within dentogingival tissues and that these specific populations have different influences on the epithelium. Our data suggest that a downregulation of Wnt signalling within PDL may be important in maintaining the integrity and anatomical position of the JE.

Assessment of proliferating cell nuclear antigen (PCNA) expression at the invading front of oral squamous cell carcinoma.

BACKGROUND: Accurate prediction of the behaviour of oral squamous cell carcinoma (OSCC) is necessary to determine prognosis and provide appropriate treatment. Therefore, it is important to investigate potential prognostic markers to determine their predictive ability. Histological assessment of specific features at the invading front of oral squamous cell carcinomas has shown to provide accurate and reproducible prognostic information. Proliferating cell nuclear antigen (PCNA) is a nuclear marker known to reflect cell turnover and may be used as a marker for tumour aggressiveness. METHODS: Twenty cases of OSCC were histologically assessed to evaluate the correlation between proliferating cell nuclear antigen expression and invasive front grading. Each case was first assessed on a haematoxylin and eosin stained slide and an invading front grading (IFG) score was determined. In order to obtain a PCNA score, immunohistological staining was carried out using the peroxidase-labelled streptavidin-biotin technique with the monoclonal antibody PC10. RESULTS: In all cases, tumour islands had a periphery of intensely stained proliferating cell nuclear antigen-positive epithelial cells. The average IFG score was 8 ± 1.8, and the average PCNA score was 75% ± 11.2. Regression analysis was done using data from the IFG score and PCNA score and taking the latter as the predictor variable. The Pearson correlation coefficient was 0.134, with a p-value of 0.572. CONCLUSION: Since the correlation between PCNA score and IFG score was not significant (p > 0.05), we conclude that there is no association between cell proliferation at the invading tumour front and the histological grading of OSCC.