Dileep Sharma

Bisphosphonate-related osteonecrosis of jaw (BRONJ): diagnostic criteria and possible pathogenic mechanisms of an unexpected anti-angiogenic side effect.

Recently, bisphosphonates (BPs) have been widely used in medical practice as anti-resorptive agents owing to their anti-osteoclatic action. In addition, these compounds are also used for their analgesic action and their potential anti-tumour effect. Patients treated with BPs may subsequently develop osteonecrosis of the jaw or maxillary bone after minor local trauma including dental work, recently labelled as bisphosphonate osteonecrosis of jaw (BRONJ). However, the etiopathogenic mechanisms of this pathological condition are poorly understood. Although, several pathways have been proposed for BRONJ occurrence, no single model can explain all morphological changes observed at the macro- and microscopic level. Recent research suggests that BPs may promote an anti-angiogenic effect which contributes directly to the clinical features associated with BRONJ. Remarkably, the anti-angiogenic effect promoting BRONJ might be in keeping with the anti-neoplastic action of BPs. The current review, presents clinical diagnostic criteria. In addition, based on our own experience we describe the histopathological criteria for diagnosis of BRONJ and the possible pathways which may lead to this frustrating pathological condition.

Vaccination against periodontitis: the saga continues

Periodontal disease can be considered to be one of the most common chronic inflammatory diseases inflicting humans. With the advent of advanced molecular diagnostic techniques, a better understanding of the role of specific pathogens and the contributory role of the host immune response in the initiation and progression of periodontal disease has been possible – although not completely. However, successful vaccine development that fully utilizes the current level of understanding has not yet occurred for human use. This paper reviews various in vitro, animal studies and human trials undertaken to develop a vaccine against periodontal disease, with emphases on the shortfalls of these efforts and future prospects of developing a successful vaccine against periodontal disease.

The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).

The effect of non-steroidal anti-inflammatory drugs on the osteogenic activity in osseointegration: a systematic review

Non-steroidal anti-inflammatory drugs are commonly used in implant dentistry for management of post-operative pain. The objective of this systematic review was to analyse the effect of non-steroidal anti-inflammatory drugs on the osteogenic activity of osteoblasts with an emphasis on its effect on osseointegration. A systematic literature search for in vitro, animal models, and clinical trials was conducted using Ovid, PubMed, Scopus, and Web of Science databases. Articles published since the introduction of selective COX-2 inhibitors, between January 1999 and July 2018, were selected. The integrated search followed the PRISMA statement with the following key terms: non-steroidal anti-inflammatory drug/s, titanium, osseointegration, and osteoblast. The review is registered at PROSPERO database: CRD42016051448. The titles and abstracts of each research article in the initial search (n = 875) were independently screened by two reviewers. A third independent reviewer reviewed the articles that were included by one but excluded by the other reviewer. This resulted in the cataloguing of 79 full-text manuscripts where the articles were assessed for the following criteria: the study investigates the effects of NSAIDs on osteoblasts, explores the COX pathway and its effect on osteogenic activity, and compares the effects of NSAIDs on osteoblasts with a control group. A total of 13 articles have been included for qualitative synthesis. There is a lack of consensus in the literature to explicitly conclude that there is a relationship between the use of post-operative NSAIDs and failed osseointegration; however, osseointegration does not appear to be negatively affected by NSAIDs in the human clinical studies.

Endothelial Transcriptomic Analysis

Endothelial cell activity can be studied targeting the mature cells within the tissues and blood vessels or it could be done using the precursor cells (EPC). For in vitro studies, pure EPC can be harvested from umbilical cord, peripheral blood and bone marrow. The following sections describe the methods of transcriptomic analyses of cells that can be employed to endothelial cells including its precursors.