Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts

Mayr-Wohlfart, U.; Waltenberger, Johannes; Hausser, Heinz; Kessler, S; Günther, Klaus‐Peter; Dehio, Christoph; Puhl, W.; Brenner, Rolf E.

doi:10.1016/s8756-3282(01)00690-1

Cited by 392 publications

(312 citation statements)

References 39 publications

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“…VEGF is well documented as a stimulator of vascular cells to undergo the formation of early vessels. 53,68,[86][87][88][89] The results from both our previous study 49 and this study corroborate this as the group with the highest VEGF content in both studies was also the only group to have rudimentary vessels present within the aggregate. However, in this study VEGF expression was seen to peak after 2 weeks of coculture without any osteogenic factors, whereas the group with osteogenic factors continued to have an increase in VEGF expression for up to 3 weeks of coculture.…”

Section: Discussionsupporting

confidence: 80%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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Section: Discussionsupporting

confidence: 80%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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“…Osteoblasts used in this study are able to migrate nondirectionally and in the direction of a chemotactic gradient as shown previously (6,11,13,19). When exposed to IL-1β, however, osteoblasts' basal migration and migration toward several chemotactic factors was significantly decreased.…”

Section: Discussionsupporting

confidence: 71%

“…To evaluate the influence of IL-1β on the adhesion and chemotaxis of osteoblasts, IL-1β was either added only into the lower chamber to establish an IL-1β gradient or to both upper and lower chamber to create a uniform IL-1β concentration. Growth factors and cytokines were di-luted in serum-free DMEM at concentrations that were found effective in previous studies (6,11,13,19): 10, 100 or 1000 pg/mL IL-1β, 100 ng/mL C5a, 10ng/mL PDGF-BB, 100 ng/mL IGF-1 and 100 ng/mL VEGF-A and filled in quadruplicates into the lower wells of the Boyden chamber, which was then covered by the polycarbonate filter. For negative control, DMEM alone was added to the lower well.…”

Section: Chemotaxis and Adhesion Assaymentioning

confidence: 99%

“…Further examples are the insulinlike growth factors 1 (IGF-1) and 2 (IGF-2), which stimulate the site-directed migration of MSC and osteoblasts (5,11,12). In addition to its known angiogenic effects, vascular endothelial growth factor A (VEGF-A) was found to have a dose-dependent chemotactic effect on MSC and primary human osteoblasts, in vitro, that is mediated through VEGF receptor 1 activation (13,14).…”

Section: Introductionmentioning

confidence: 99%

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IL-1β Inhibits Human Osteoblast Migration

Hengartner

Fiedler

Ignatius

et al. 2013

Mol Med

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Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1β (IL-1β), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1β may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1β affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1β significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulinlike growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1β induced an even stronger inhibition of migration and completely abolished the migratory response of osteoblasts toward PDGF-BB, IGF-1, vascular endothelial growth factor A (VEGF-A) and the complement factor C5a. IL-1β induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases (JNK) activation and inhibition of these signaling pathways suggested an involvement in the IL-1β effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1β. These results indicate that the presence of IL-1β leads to impaired recruitment of osteoblasts which might influence early stages of fracture healing and could have pathological relevance for bone remodeling in inflammatory bone disease.

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“…Initial reports suggested that these receptors were expressed only on endothelial cells (Brown et al, 1993;Detmar et al, 1994). However, more recent studies have noted these tyrosine kinase receptors on hematopoietic stem cells, monocytes, and osteoblasts (Bellamy et al, 1999;Mayr-Wohlfart et al, 2002;Lalla et al, 2003). VEGF receptors have also been noted on tumor cells, including leukemic cells, Kaposi's sarcoma, and breast carcinoma (Arora et al, 1999;Dias et al, 2000;Hasan and Jayson, 2001;Price et al, 2001;Ryden et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

et al. 2005

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Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts

Cited by 392 publications

References 39 publications

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

IL-1β Inhibits Human Osteoblast Migration

Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

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