Our data suggest that T cells support spontaneous osteoclastogenesis in PP via RANKL and TNF-alpha overexpression.
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.
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.
Peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) is a transcription coactivator that interacts with a broad range of transcription factors involved in several biological responses. Here, we show that PGC1α plays a role in skeletal homeostasis since aged PGC1α-deficient mice (PGC1α) display impaired bone structure. Micro-CT of the tibial mid-shaft showed a marked decrease of cortical thickness in PGC1α (- 11.9%, p < 0.05) mice compared to wild-type littermate. Trabecular bone was also impaired in knock out mice which displayed lower trabecular thickness (Tb.Th) (- 5.9% vs PGC1α, p < 0.05), whereas trabecular number (Tb.N) was higher than wild-type mice (+ 72% vs PGC1α, p < 0.05), thus resulting in increased (+ 31.7% vs PGC1α, p < 0.05) degree of anisotropy (DA), despite unchanged bone volume fraction (BV/TV). Notably, these impairments of cortical and trabecular bone led to a dramatic ~ 48.4% decrease in bending strength (p < 0.01). These changes in PGC1α mice were paralleled by a significant increase in osteoclast number at the cortical bone surface and in serum level of the bone resorption marker, namely, C-terminal cross-linked telopeptides of type I collagen (CTX-I). We also found that in cortical bone, there was lower expression of mRNA codifying for the key bone-building protein Osteocalcin (Ocn). Interestingly, Collagen I mRNA expression was reduced in mesenchymal stem cells from bone marrow of PGC1α, thus indicating that differentiation of osteoblast lineage is downregulated. Overall, results presented herein suggest that PGC1α may play a key role in bone metabolism.
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.
Obstructive sleep apnea syndrome (OSAS) is a phenomenon of repeated, episodic reduction, or cessation of airflow (hypopnea/apnea) as a result of upper airways obstruction. First-line treatment in younger children is adenotonsillectomy, although other available treatment options in middle-aged adults include continuous positive airways pressure (CPAP) and airway adjuncts. Oral appliances (OA) are a viable treatment alternative in patients with OSAS.The objective of this study was to assess, in a 1-year follow-up study, an OA in OSAS patients. The participants were subjected to polysomnographic examination with a validated device (MicroMESAM). Eight participants were fitted with a Thornton Adjustable Positioner (TAP). The participants were asked to wear the test appliance for 7 nights, and in case of compliance, for 6 months. The selected patients record their usage of the appliance and any adverse effects in a treatment journal. The research focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index) and the effect of oral appliances on daytime function.In conclusion, the results suggest that OA have a definite role in the treatment of snoring and sleep apnea.
It is well known dental reimplantation is indicated following traumatic avulsion by the preservation of cellular vitality in the periodontal ligament and under conditions of asepsis. The rate of endodontic success at five years reported in the literature ranges between 70% and 91%. However, intentional dental reimplantation is an effective strategy for the treatment of teeth that would be difficult, if not impossible, to treat using traditional root canal therapy. Different prognoses exist for intentional dental reimplantation and trauma-related reimplantation. This is due to such important variables such as the level of cellular vitality in the periodontal ligament; the degree of trauma to surrounding tissues, and the degree of asepsis when a tooth is removed. Surgical extraction is more favorable in this regard compared to a traumatic avulsion scenario. This paper presents a report of an intentional dental reimplantation of a maxillary right firstmolar.
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