RANKL promotes osteoblastic activity in vascular smooth muscle cells by upregulating endothelial BMP-2 release
| Autor: | Hannah Forde, Colin Davenport, Philip M. Cummins, Keith D. Rochfort, Ronan P. Murphy, Diarmuid Smith, Emma Harper |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male musculoskeletal diseases 0301 basic medicine medicine.medical_specialty Vascular smooth muscle Population Bone Morphogenetic Protein 2 030204 cardiovascular system & hematology Bone morphogenetic protein Biochemistry Bone morphogenetic protein 2 Muscle Smooth Vascular Young Adult 03 medical and health sciences Paracrine signalling 0302 clinical medicine Osteoprotegerin Internal medicine medicine Humans Noggin education education.field_of_study Osteoblasts biology Chemistry RANK Ligand Endothelial Cells Cell Biology 030104 developmental biology Endocrinology RANKL cardiovascular system biology.protein Female |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 77:171-180 |
| ISSN: | 1357-2725 |
| Popis: | Introduction Receptor activator of nuclear factor kappa beta-ligand (RANKL) is thought to promote vascular calcification (VC) by inducing osteoblastic behaviour in vascular smooth muscle cells (VSMC) in an ill-defined process. The present study assessed whether RANKL affects pro-osteoblastic paracrine signalling between human aortic endothelial cells (HAEC) and human aortic smooth muscle cells (HASMC) using both conditioned media transfer and cell co-culture experimental approaches. Methods and results For initial experiments (6-well format), HAEC-conditioned media was harvested following 72 h exposure to RANKL, and transferred to reporter HASMCs with/without noggin, an inhibitor of pro-osteoblastic bone morphogenetic protein (BMP) paracrine signalling. In further experiments, HAECs and HASMCs were co-cultured within the CellMax® Duo, a perfusing bioreactor unit that mimics the flow-mediated co-interaction of these cells within the arterial wall, and RANKL was added to the perfusing media for 72 h. At the conclusion of each experiment markers of osteoblastic activity were measured in HASMCs, including alkaline phosphatase (ALP) activity, mRNA levels of ALP and Runx2, as well as BMP-2 and BMP-4 concentrations. RANKL increased BMP-2 release from HAECs, while exposure of HASMCs to RANKL-treated HAEC-conditioned media induced osteoblastic behaviour in HASMCs, an effect prevented by noggin. Within the CellMax® Duo bioreactor, the addition of RANKL to the intraluminal HAECs also produced an increase in BMP-2 and increased osteoblastic behaviour within the co-cultured HASMC population. Conclusions RANKL promotes VC by inducing BMP-2 release from HAECs, which in turn appears to act in a paracrine fashion on the adjacent HASMC population to increase osteoblastic activity. |
| Databáze: | OpenAIRE |
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