N Cirulli

Bio: N Cirulli is an academic researcher from University of Bari. The author has contributed to research in topics: Osteoclast & Bone resorption. The author has an hindex of 8, co-authored 17 publications receiving 352 citations.

Alendronate Reduces Adhesion of Human Osteoclast-like Cells to Bone and Bone Protein-Coated Surfaces

Abstract: Bisphosphonates (BPs) are potent inhibitors of bone resorption and are therapeutically effective in disease of increased bone turnover, but their mechanism(s) of action remain to be elucidated. Using as experimental model human osteoclast-like cell lines derived from giant cell tumors of bone, extensively characterized for their osteoclast features, we investigated the adhesive properties of osteoclasts on bone slices and on different proteins of the extracellular matrix in the presence of BPs. Adhesion assays using bone slices pretreated with ALN, at the established active concentration, showed that, although the morphology of osteoclasts plated onto pretreated bone slices was not modified, the number of adherent cells was reduced by the treatment of about 50% vs. controls. The effect of ALN on the adhesion of osteoclast-like cells onto specific extracellular matrix proteins, such as bone sialoprotein-derived peptide, containing the RGD sequence, conjugated to BSA (BSP-BSA) and fibronectin (FN), was also tested. In the case of FN the treatment with ALN of protein-coated wells did not modify the percentage of cell adhesion compared with the control, whereas onto BSP-BSA the presence of ALN significantly reduced adhesion of about 40-45%, suggesting that the inhibitory effect of ALN on cell adhesion could probably be due to the interference with receptors specifically recognizing bone matrix proteins as alphaVbeta3 integrins. Furthermore, ALN induced Ca-mediated intracellular signals in osteoclasts, triggering a 2-fold increase in intracellular calcium concentration.

Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFα, and IL‐7 in an in vitro model derived from human psoriatic arthritis

Abstract: Psoriatic arthritis (PsA) is an inflammatory joint disease, characterized by extensive bone resorption, whose mechanisms have not been fully elucidated. Thus, in the present study we investigated the involvement of RANKL, TNFalpha, and IL-7 in the osteoclastogenesis of PsA patients. In vitro osteoclastogenesis models, consisting of unfractionated and T-cell-depleted mononuclear cells from peripheral blood (PBMCs) and synovial fluid (SFMCs) of 20 PsA patients as well as from healthy donors were studied. Freshly isolated T and B cells from PBMCs and T cells and fibroblasts from SFMCs of PsA patients were subjected to RT-PCR to detect the levels of RANKL, TNFalpha, and IL-7. Osteoclastogenesis was studied in the presence of RANK-Fc, anti-TNFalpha, and anti IL-7 functional antibodies. We demonstrate that lymphocytes and fibroblasts support osteoclast (OC) formation in PsA patients through the production of osteoclastogenic cytokines. In particular, OC formation was completely abolished in unstimulated T cell-depleted PBMC cultures, and reduced by approximately 70% in unstimulated T cell-depleted SFMC cultures. Freshly isolated T cells from PBMCs and SFMCs of PsA patients overexpressed RANKL and TNFalpha, while fibroblasts from synovial fluid produced only RANKL. We show that the presence of RANK-Fc and/or anti-TNFalpha functional antibodies reduced OC formation. Moreover, T and B cells from PBMCs as well as T cells and fibroblasts from SFMCs expressed IL-7 mRNA. Finally, the anti-IL-7 functional antibody significantly reduced osteoclastogenesis. Our results suggest that fibroblasts, B and T lymphocytes support OC formation by producing RANKL, TNFalpha, and IL-7, contributing to the aggressive bone resorption in PsA patients.

T Cells Support Osteoclastogenesis in an In Vitro Model Derived From Human Periodontitis Patients

Abstract: Background: Periodontitis is characterized by alveolar bone destruction; however, the mechanisms responsible for bone damage are poorly understood. It has been reported that T cells are implicated in the pathogenesis of periodontitis. It has been also demonstrated that activated T lymphocytes secrete receptor activator of nuclear factor-kappa B ligand (RANKL) and can support the differentiation of monocytes into resorbing osteoclasts (OCs). Therefore, the purpose of this study was to examine the OC formation in periodontitis patients (PP) and the role of T cells in osteoclastogenesis.Methods: To study OC formation, we used an in vitro model consisting of unstimulated and unfractionated peripheral blood mononuclear cells (PBMCs) from PP and controls. In parallel, T-cell–depleted PBMCs from the same patients were also established. The expression of RANKL and tumor necrosis factor-alpha (TNF-α) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot in fresh T cells isolated...

Periodontal disease and bone pathogenesis: the crosstalk between cytokines and porphyromonas gingivalis.

Abstract: Periodontal disease is the most frequent cause of tooth loss among adults. It is defined as a plaque-induced inflammation of the periodontal tissues that results in a loss of support of the affected teeth. This process is characterized by destruction of the periodontal attachment apparatus, increased bone resorption with loss of crestal alveolar bone, apical migration of the epithelial attachment, and formation of periodontal pockets. Although the presence of periodontal pathogens such as Porphyromonas gingivalis is a prerequisite, the progression of periodontal disease is dependent on the host response to pathogenic bacteria that colonize the tooth surface. Nowadays, a growing body of literature has accumulated to investigate the association between bone diseases, periodontal pathogens and periodontal diseases. The integration of pathogen-associated molecular patterns from microorganisms with their surface receptors in the immune cells, induces the production of several cytokines and chemokines that present either a pro- and/or anti-inflammatory role and the activation of mechanisms of controlling this and the related disease, such as osteoporosis and rheumatoid arthritis. This review focuses on the evidence and significance of bone host cell invasion by Porphyromonas gingivalis in the pathogenesis of bone disorders, as well as the different lines of evidence supporting the role of cytokines in bone diseases.

Education Technology in Orthodontics and Paediatric Dentistry during the COVID-19 Pandemic: A Systematic Review.

Abstract: Over the last decade, medical education changed from traditional teaching methods to telematic and networking scholar and e-learning approach. The objective of the present systematic review was to evaluate the effectiveness and teachers/student's acceptability of e-learning applied to the field of orthodontics and paediatric dentistry. A database search of the literature was conducted on PubMed and Embase databases from January 2005 to May 2021. A total of 172 articles were identified by the electronic search, while a total of 32 papers were selected for qualitative analysis. Overall, 19 articles investigated the effectiveness of e-learning, and no difference of acceptability was reported between e-learning and traditional methods for a wide part of the articles selected. A total of 25 papers provided a satisfaction questionnaire for learners and all were positive in their attitude towards e-learning. The results showed that e-learning is an effective method of instruction, complementing the traditional teaching methods, and learners had a positive attitude and perception. The evidence of the present study reported a high level of acceptability and knowledge level of e-learning techniques, compared to frontal lecture methods, in the fields of orthodontics and paediatric dentistry.

Cellular and molecular mechanisms of action of bisphosphonates

Abstract: BACKGROUND Bisphosphonates currently are the most important class of antiresorptive agents used in the treatment of metabolic bone diseases, including tumor-associated osteolysis and hypercalcemia, Paget's disease, and osteoporosis. These compounds have high affinity for calcium and therefore target to bone mineral, where they appear to be internalized selectively by bone-resorbing osteoclasts and inhibit osteoclast function. METHODS This article reviews the pharmacology of bisphosphonates and the relation between the chemical structure of bisphosphonates and antiresorptive potency, and describes recent new discoveries of their molecular mechanisms of action in osteoclasts. RESULTS Bisphosphonates can be grouped into two pharmacologic classes with distinct molecular mechanisms of action. Nitrogen-containing bisphosphonates (the most potent class) act by inhibiting the mevalonate pathway in osteoclasts, thereby preventing prenylation of small GTPase signaling proteins required for osteoclast function. Bisphosphonates that lack a nitrogen in the chemical structure do not inhibit protein prenylation and have a different mode of action that may involve the formation of cytotoxic metabolites in osteoclasts or inhibition of protein tyrosine phosphatases. CONCLUSIONS Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect osteoclasts. After more than 30 years of clinical use, their molecular mechanisms of action are only just becoming clear. Cancer 2000;88:2961–78. © 2000 American Cancer Society.

Novel antiangiogenic effects of the bisphosphonate compound Zoledronic Acid

Abstract: Bisphosphonate drugs inhibit osteoclastic bone resorption and are widely used to treat skeletal complications in patients with tumor-induced osteolysis. We now show that zoledronic acid, a new generation bisphosphonate with a heterocyclic imidazole substituent, is also a potent inhibitor of angiogenesis. In vitro, zoledronic acid inhibits proliferation of human endothelial cells stimulated with fetal calf serum, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (IC(50) values 4.1, 4.2, and 6.9 microM, respectively), and modulates endothelial cell adhesion and migration. In cultured aortic rings and in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. When administered systemically to mice, zoledronic acid potently inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF [ED(50), 3 microg/kg (7.5 nmol/kg) s.c.]. These findings indicate that zoledronic acid has marked antiangiogenic properties that could augment its efficacy in the treatment of malignant bone disease and extend its potential clinical use to other diseases with an angiogenic component.

Inflammatory bone loss: pathogenesis and therapeutic intervention.

Abstract: Bone continuously undergoes building and degradation — a process known as bone remodelling This tightly controlled process can be dysregulated by chronic inflammation, and bone loss is commonly associated with inflammatory diseases Here, Redlich and Smolen discuss the molecular mechanisms mediating the inflammatory loss of bone and present strategies and agents for therapeutic intervention Bone is a tissue undergoing continuous building and degradation This remodelling is a tightly regulated process that can be disturbed by many factors, particularly hormonal changes Chronic inflammation can also perturb bone metabolism and promote increased bone loss Inflammatory diseases can arise all over the body, including in the musculoskeletal system (for example, rheumatoid arthritis), the intestine (for example, inflammatory bowel disease), the oral cavity (for example, periodontitis) and the lung (for example, cystic fibrosis) Wherever inflammatory diseases occur, systemic effects on bone will ensue, as well as increased fracture risk Here, we discuss the cellular and signalling pathways underlying, and strategies for therapeutically interfering with, the inflammatory loss of bone

Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds.

Abstract: This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions.

How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis

Abstract: Preshaw PM, Taylor JJ. How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol 2011; 38 (Suppl. 11): 60–84. doi: 10.1111/j.1600-051X.2010.01671.x. Abstract Objective: To review current knowledge on cytokine interactions and the cytokine-mediated links between innate and adaptive immunity that are relevant to the pathophysiology of periodontitis. Materials and Methods: A structured review of the literature was undertaken to identify relevant research publications using a Medline search from 1950 to September 2010. The focus of the search was on the functional role of cytokines, i.e. their actions and responses relevant to the pathogenesis of periodontal disease rather than more descriptive studies of their expression in tissues and body fluids. It was not possible to conduct a traditional systematic review with a focussed question due to the heterogeneity of published research. Results: There is enormous heterogeneity in the periodontal literature in terms of experimental approaches. We have the deepest understanding of the role of the pro-inflammatory cytokines [e.g. interleukin (IL)-1β, tumour necrosis factor-α, IL-6] with accumulating data on T-cell regulatory cytokines (e.g. IL-12, IL-18), chemokines and cytokines which mediate bone cell development and function (e.g. receptor activator of NF-κB ligand, osteoprotegerin). It is clear that there are multiple, overlapping and complex functional links between cytokines with regulatory control exerted at a number of levels and involving numerous cell types (both immune cells and resident cells in the periodontium). Conclusion: Cytokines appear to interact functionally in networks in the periodontium and integrate aspects of innate and adaptive immunity. However, our understanding is far from complete, particularly how molecular and cellular pathways relate to disease pathogenesis. We should adopt consistent experimental approaches to gain better insight into the totality of cytokine networks and how they drive immune responses in the periodontium.