Systemic Regulation of Distraction Osteogenesis: A Cascade of Biochemical Factors

Weiß, Stefan; Baumgart, R; Jochum, Marianne; Strasburger, C. J.; Bidlingmaier, Martin

doi:10.1359/jbmr.2002.17.7.1280

Cited by 66 publications

(35 citation statements)

References 36 publications

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“…The lack of complete regeneration might be due to a prolonged ossification process, but also because of the missing mechanical loading (Simpson et al 1996, Sato et al 1999, Weiss et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Sequential changes in vessel formation and micro-vascular function during bone repair

et al. 2006

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Background Angiogenesis, the process of new vessel formation from a pre-existing vascular network, is essential for bone development and repair. New vessel formation and microvascular functions are crucial during bone repair, not only for sufficient nutrient supply, transport of macromolecules and invading cells, but also because they govern the metabolic microenvironment. Despite its central role, very little is known about the initial processes of vessel formation and microvascular function during bone repair.Methods To visualize and quantify the process of vessel formation and microvascular function during bone repair, we transplanted neonatal femora with a substantial defect into dorsal skin-fold chambers in severe combined immunodeficient (SCID) mice for continuous noninvasive in-vivo evaluation. We employed intravital microscopic techniques to monitor effective microvascular permeability, functional vascular density, blood flow rate and leukocyte flux repeatedly over 16 days. Oxytetracyclin and v. Kossa/v. Giesson staining was performed to quantify the calcification process in vivo and in vitro.Results Development of a hematoma surrounding the defect area was the initial event, which was accompanied by a significant increase in microvascular permeability and blood flow rate. With absorption of the hematoma and vessel maturation, permeability decreased continuously, while vascular density and tissue perfusion increased. Histological evaluation revealed that the remodeling of the substantial defect prolonged the invivo monitored calcification process.

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Section: Discussionmentioning

confidence: 99%

Sequential changes in vessel formation and micro-vascular function during bone repair

et al. 2006

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“…TGF-PI is a potential chemotactic stimulator for bone cells and promotes biosynthesis of extracellular matrix [30]. This growth factor actively regulated chondrogenesis and osteogenesis in bone regeneration [6,9,45]. The results of RT-PCR and immuno-histochemistry demonstrated that TGF-PI expression was elevated after ESW treatment.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

Chen

Wurtz

Wang

et al. 2004

Journal Orthopaedic Research

170

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Extracorporeal shock wave (ESW) treatment has recently been established as a method to enhance bone repair. Here, we reported that ESW-promoted healing of segmental defect via stimulation of mesenchymal stem cell recruitment and differentiation into bone forming cells. Rats with a segmental femoral defect were exposed to a single ESW treatment (0.16 mJ/mm?, 1 Hz, 500 impulses). Cell morphology and histological changes in the defect region were assessed 3, 7, 14, and 28 days post-treatment. Presence of mesenchymal stem cell was assayed by immuno-staing for RPS9, a recently discovered marker, and also production of TGF-PI and VEGF was monitored. ESW treatment increased total cell density and the proportion of RP59 positive cells in the defect region. High numbers of round-and cuboidal-shaped cells strongly expressing RPS9 were initially found. Later, the predominant cell type was spindle-shaped fibroblastic cells, subsequently, aggregates of osteogenic and chondrogenic cells were observed. Histological observation suggested that bone marrow stem cells were progressively differentiated into osteoblasts and chondrocytes. RP59 staining was initially intense and decreased with the appearance of expression depended on the differentiation states of osteogenic and chondrogenic cells during the regeneration phase. Mature chondrocytes and osteoblasts exhibited only slight RP59 immunoreactivity. Expression of TGF-PI and VEGF-A mRNA in the defect tissues was also significantly increased ( P < 0.05) after ESW treatment as determined by RT-PCR. Intensive TGF-PI immuno-reactivity was induced immediately, whereas a lag period was observed for VEGF-A. Chondrocytes and osteoblasts at the junction of ossified cartilage clearly exhibited VEGF-A expression. Our findings suggest that recruitment of meseoblasts at the junction of ossified cartilage clearly exhibited mesenchymal stem cells is a critical step in bone reparation that is enhanced by ESW treatment. TGF-P1 and VEGF-A are proposed to play a chemotactic and mitogenic role in recruitment and differentiation of mesenchymal stem cells.

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“…These include sustained proliferation of osteoblast progenitor cells in the center of the distraction gap (Aronson et al, 1997;Li et al, 1997), marked increases in blood flow and vascular proliferation in the region (Aronson, 1994;Choi et al, 2000;Rowe et al, 1999), and upregulation within the gap of growth factors and matrix proteins involved in bone formation (e.g. TGFβ-1, BMP-2, BMP-4, IGF I, bFGF, OPN) Liu et al, 1999;Mehrara et al, 1999;Rauch et al, 2000;Sato et al, 1999;Sato et al, 1998;Weiss et al, 2002). Similar results have been reported for experiments in which the lengthening phase of DO is compared to healing following a simple osteotomy (no distraction) (Aronson et al, 1997;Lammens et al, 1998;Weiss et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…TGFβ-1, BMP-2, BMP-4, IGF I, bFGF, OPN) Liu et al, 1999;Mehrara et al, 1999;Rauch et al, 2000;Sato et al, 1999;Sato et al, 1998;Weiss et al, 2002). Similar results have been reported for experiments in which the lengthening phase of DO is compared to healing following a simple osteotomy (no distraction) (Aronson et al, 1997;Lammens et al, 1998;Weiss et al, 2002). While many of these studies have suggested that these osteogenic phenomena are associated with the "tension-stress" created by the distraction process, little formal quantification of the physical environment within the distraction gap has been performed.…”

Section: Introductionmentioning

confidence: 99%

Relationships between tissue dilatation and differentiation in distraction osteogenesis

2006

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Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

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Systemic Regulation of Distraction Osteogenesis: A Cascade of Biochemical Factors

Cited by 66 publications

References 36 publications

Sequential changes in vessel formation and micro-vascular function during bone repair

Sequential changes in vessel formation and micro-vascular function during bone repair

Recruitment of mesenchymal stem cells and expression of TGF‐β1 and VEGF in the early stage of shock wave‐promoted bone regeneration of segmental defect in rats

Relationships between tissue dilatation and differentiation in distraction osteogenesis

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