Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition

Songia, Paola; Branchetti, Emanuela; Parolari, Alessandro; Myasoedova, Veronika A.; Ferrari, Giovanni; Alamanni, Francesco; Tremoli, Elena; Poggio, Paolo

doi:10.1016/j.yjmcc.2016.06.061

Cited by 23 publications

(29 citation statements)

References 36 publications

(50 reference statements)

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“…PRF, however, did not induce expression of Tnfrsf11b mRNA in non-osteoblastic NIH3T3 fibroblasts (Fig. 1E), although non-osteoblastic cells, such as gingival fibroblasts (35), adipocytes (36), and endothelial cells (37), can produce OPG. PRF also increased the ratio of OPG-encoding mRNA to RANKL-encoding mRNA in these cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

et al. 2019

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Platelet-rich fibrin (PRF) is a platelet concentrate derived from complete autologous blood rich in growth factors in the fibrin matrix. Although PRF has been used during oral surgery to optimize wound healing in soft and hard tissue, the precise role of PRF in bone healing remains unclear. The present study assessed the role of PRF in bone remodeling. PRF was prepared from whole blood by low speed centrifugation without any anti-coagulants. Culture of MC3T3-E1 cells with PRF induced the expression of osteoprotegerin (OPG), but had no effect on the expression of receptor activator of nuclear factor-κB ligand (RANKL), increasing the OPG/RANKL ratio. Expression of other osteoblastic differentiation makers, including BMP-2 and −4 and RUNX2, was not affected. PRF filling of a hole defect in the mental foramen bone of rats increased OPG positivity and decreased tartrate-resistant acid phosphatase positivity compared with unfilled control. In conclusion, PRF increased the OPG/RANKL ratio by inducing OPG expression, suggesting that PRF enhances early stage osteogenesis by optimizing osteoblastic differentiation. The present study provides a scientific basis for clinical findings showing that PRF can enhance bone regeneration such as sinus lift.

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Section: Resultsmentioning

confidence: 95%

Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

et al. 2019

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“…The overexpression of OPG has been demonstrated during EndMT and linked to autocrine effects characterized by the increased production of ROS. OPG interferes with correct valve endothelial function by increasing proteoglycan and matrix metalloproteases (MMPs) levels [39].…”

Section: Interactions Between Opg/rankl/rank and Endogenous Factormentioning

confidence: 99%

The Role of Osteoprotegerin and Its Ligands in Vascular Function

Rochette

Méloux

Rigal

et al. 2019

IJMS

112

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The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular components and modify gene expression. Cytokine production and activation of their receptors induce mechanisms to recruit monocytes and neutrophils as well as endothelial cells. Data support the role of an increased OPG/RANKL ratio as a possible marker of progression of endothelial dysfunction in metabolic disorders in relationship with inflammatory marker levels. We review the role of the OPG/RANKL/RANK triad in vascular function as well as molecular mechanisms related to the etiology of vascular diseases. The potential therapeutic strategies may be very promising in the future.

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“…Recently, we showed that OPG was involved in mitral valve endothelial to mesenchymal transition and plasma OPG levels permitted to identify MVP patients with an AUC of 0.92 [ 8 ]. However, all the selected MVP patients had only posterior MVP.…”

Section: Discussionmentioning

confidence: 99%

“…Given the background, we investigated Osteoprotegerin (OPG), a well-known protein linked to oxidative stress status [ 7 ] and to endothelial mesenchymal transition on endothelial cells isolated from MVP patients [ 8 ]. OPG is a secretory glycoprotein of the tumour necrosis factor receptor superfamily involved in calcification, apoptosis, proliferation, and migration processes [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model

Songia

Porro

Chiesa

et al. 2017

Oxidative Medicine and Cellular Longevity

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Background. Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. Besides echocardiography, up to now there are no reliable biomarkers available for the identification of this pathology. We aim to generate a predictive model, based on circulating biomarkers, able to identify MVP patients with the highest accuracy. Methods. We analysed 43 patients who underwent mitral valve repair due to MVP and compared to 29 matched controls. We assessed the oxidative stress status measuring the oxidized and the reduced form of glutathione by liquid chromatography-tandem mass spectrometry method. Osteoprotegerin (OPG) plasma levels were measured by an enzyme-linked immunosorbent assay. The combination of these biochemical variables was used to implement several logistic regression models. Results. Oxidative stress levels and OPG concentrations were significantly higher in patients compared to control subjects (0.116 ± 0.007 versus 0.053 ± 0.013 and 1748 ± 100.2 versus 1109 ± 45.3 pg/mL, respectively; p < 0.0001). The best regression model was able to correctly classify 62 samples out of 72 with accuracy in terms of area under the curve of 0.92. Conclusions. To the best of our knowledge, this is the first study to show a strong association between OPG and oxidative stress status in patients affected by MVP with severe regurgitation.

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Mitral valve endothelial cells secrete osteoprotegerin during endothelial mesenchymal transition

Cited by 23 publications

References 36 publications

Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

Platelet‑rich fibrin increases the osteoprotegerin/receptor activator of nuclear factor‑κB ligand ratio in osteoblasts

The Role of Osteoprotegerin and Its Ligands in Vascular Function

Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model

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