Osteoclasts are important for bone angiogenesis
ABSTRACT Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-kappaB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9(-/-) mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.
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ABSTRACT: Bone marrow (BM) contains hematopoietic stem cells (HSCs) and nonhematopoietic cells. HSCs give rise to all types of mature blood cells, while the nonhematopoietic component includes osteoblasts/osteoclasts, endothelial cells (ECs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). These cells form specialized "niches" which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche", rich in blood vessels where ECs and mural cells (pericytes and smooth muscle cells), create a microenvironment affecting the behavior of several stem and progenitor cells. The vessel wall acts as an independent niche for the recruitment of EPCs and MSCs. This chapter will focus on the description of the role of BM niches in the control of angiogenesis occurring during multiple myeloma progression. Copyright © 2015 Elsevier Inc. All rights reserved.International review of cell and molecular biology 01/2015; 314:259-82. DOI:10.1016/bs.ircmb.2014.10.004 · 4.52 Impact Factor
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ABSTRACT: Bone marrow contains hematopoietic stem cells (HSCs) and non hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells and mesenchymal stem cells. All of these cells form specialized "niches" which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels where endothelial cells and mural cells (pericytes and smooth muscle cells) create a microenvironment that affects the behavior of several stem and progenitor cells. The vessel wall serves as an independent niche for the recruitment of endothelial progenitor cells, mesenchymal stem cells and HSCs. The activation by angiogenic factors and inflammatory cytokines switch of the "vascular niche" promote tumor growth. This review article will focus on the description of the mechanisms involved in the generation of signals released by endothelial cells in the "vascular niche" that promote tumor growth in multiple myeloma.Frontiers in Bioscience 01/2014; 19:304-11. · 4.25 Impact Factor
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ABSTRACT: Flow through a rectangular enclosure with a central partition provides a convenient means of understanding the flow through passenger-car-cabins, clean rooms, operation theatres and other enclosed spaces. Flow through such a system is complex, i.e., three dimensional, turbulent and has low mean velocity. The present experimental investigation involves measuring the complete flow field by the use of a five-holed probe and is aimed at studying the flow field deflection due to the presence of a fixed central partition. Vector plots in vertical planes perpendicular to the longitudinal and transverse axes of the enclosure are discussed. The available measurements indicate that as the jet approaches the partition, the flow is deflected upwards. However behind the partition, the jet fills up the enclosure with forward flow in the central region enveloped by regions of reverse flow at the top and bottomEnergy Conversion Engineering Conference, 1997. IECEC-97., Proceedings of the 32nd Intersociety; 01/1997