Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: Implications for distraction osteogenesis

Cillo, Joseph E.; Gaßner, Robert; Koepsel, Richard R.; Buckley, Michael

doi:10.1067/moe.2000.107531

Cited by 96 publications

(63 citation statements)

References 27 publications

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“…In skeletal muscle cells and osteoblast-like cells, mechanical stretch increased FGF-2 expression (7,35), but other models that generate mechanical stretch did not find an effect on FGF-2 expression in the heart, in skeletal muscle, or in mesangial cells (14,30,55). Our results are the first to demonstrate that mechanical stretch increases the expression of FGF-2 mRNA in vascular smooth muscle cells.…”

Section: Discussionsupporting

confidence: 47%

Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells

Quinn

Schlueter

Soifer

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Vascular endothelial growth factor (VEGF) and basic (b) fibroblast growth factor (FGF-2/bFGF) are involved in vascular development and angiogenesis. Pulmonary artery smooth muscle cells express VEGF and FGF-2 and are subjected to mechanical forces during pulsatile blood flow. The effect of stretch on growth factor expression in these cells is not well characterized. We investigated the effect of cyclic stretch on the expression of VEGF and FGF-2 in ovine pulmonary artery smooth muscle cells. Primary confluent cells from 6-wk-old lambs were cultured on flexible silicon membranes and subjected to cyclic biaxial stretch (1 Hz; 5–25% stretch; 4–48 h). Nonstretched cells served as controls. Expression of VEGF and FGF-2 was determined by Northern blot analysis. Cyclic stretch induced expression of both VEGF and FGF-2 mRNA in a time- and amplitude-dependent manner. Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold). These results demonstrate that mechanical stretch regulates VEGF and FGF-2 gene expression, which could play a role in pulmonary vascular development or in postnatal pulmonary artery function or disease.

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Section: Discussionsupporting

confidence: 47%

Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells

Quinn

Schlueter

Soifer

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This conclusion was based on our observations that the exogenous addition of 1 ng/ml TGF-β to the static tension wild-type gels caused them to contract far more than the Dcn −/− gels (data not shown). However, because cyclic strain is reported to upregulate the the synthesis of TGF-β [17], we believe that the differences reported in this study were caused by the interactions between decorin, TGF-β, and cyclic strain, but not due to free TGF-β alone.…”

Section: Discussioncontrasting

confidence: 46%

“…This same influence was not apparent in the control gels grown with wild-type cells, in which the endogenously produced TGF-β was sequestered by the cell secreted decorin, but the exogenous addition of TGF-β made the characteristics of the control gels similar to those of the Dcn −/− cell-seeded gels. Given that expression of collagen, PGs, and TGF-β is mechanosensitive [8,13,14,17], it is unclear how mechanical stimulation would influence the organization of collagen matrices in the absence of decorin. Therefore, in this paper, collagen matrices containing embryonic fibroblasts from Dcn −/− and wild-type control mouse embryos were used as a platform to investigate the effects of the presence or absence of decorin and cyclic mechanical strain on matrix organization and material behavior.…”

Section: Introductionmentioning

confidence: 99%

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

et al. 2008

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Cyclic strain evokes the expression of the small leucine-rich proteoglycans decorin and biglycan in 2-D cultures and native tissues. However, strain dependent expression of these proteoglycans has not been demonstrated in engineered tissues. We hypothesized that the absence of decorin may compromise the effect of cyclic strain on the development of engineered tissues. Thus, we investigated the contribution of decorin to tissue organization in cyclically-strained collagen gels relative to statically-cultured controls. Decorin null (Dcn −/− ) and wild-type murine embryonic fibroblasts were seeded within collagen gels and mechanically conditioned using a Flexcell ® Tissue Train ® culture system. After eight days, the cyclically-strained samples demonstrated greater collagen fibril density, proteoglycan content, and material strength for both cell types. On the other hand, increases in cell density, collagen fibril diameter, and biglycan expression were observed only in the cyclically-strained gels seeded with Dcn −/− cells. Although cyclic strain caused an elevation in proteoglycan expression regardless of cell type, the type of proteoglycan differed between groups: the Dcn −/− cell-seeded gels produced an excess of biglycan not found in the wild-type controls. These results suggest that decorin-mediated tissue organization is strongly dependent upon tissue type and mechanical environment.

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“…Early cellular proliferation above the cortex appears to make a crucial difference in callus size. Several studies have demonstrated that mechanical forces stimulate the expressions of growth factors [7,30]. Li et al reported that FGF-2 synthesis results from an immediate-early gene induced by mechanical stress in osteogenic cells [17].…”

Section: Discussionmentioning

confidence: 99%

Influence of Internal Fixator Stiffness on Murine Fracture Healing: Two Types of Fracture Healing Lead to Two Distinct Cellular Events and FGF-2 Expressions

et al. 2011

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This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix™ plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix™ plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments. Key words: callus formation, fracture, growth factor, internal fixator, mouse

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Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: Implications for distraction osteogenesis

Cited by 96 publications

References 27 publications

Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells

Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells

Influence of cyclic strain and decorin deficiency on 3D cellularized collagen matrices

Influence of Internal Fixator Stiffness on Murine Fracture Healing: Two Types of Fracture Healing Lead to Two Distinct Cellular Events and FGF-2 Expressions

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