Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7 during distraction osteogenesis in rabbits

Rauch, Frank; Lauzier, Dominique; Croteau, Sylvie; Travers, Rose; Glorieux, Francis H.; Hamdy, Reggie C.

doi:10.1016/s8756-3282(00)00337-9

Cited by 140 publications

(110 citation statements)

References 21 publications

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“…Further, only one set of material properties was used for both the regenerate and medullary tissue. This rendered the analysis most applicable to the early stages of the distraction phase, when only granular and loose connective tissues, rather than mineralized tissues, are present in the regenerate (Rauch et al, 2000;Tay et al, 1998). We also assumed that the tissues did not become damaged during distraction.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relationships between tissue dilatation and differentiation in distraction osteogenesis

2006

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“…3,4 Recently, several animal studies have described the expression patterns of BMPs during distraction osteogenesis in long bones or mandibles. [5][6][7] BMPs were shown to play vital roles in governing new bone formation after osteodistraction. Therefore, introducing BMPs into the distraction gap may be a reasonable approach to accelerate callus formation.…”

Section: Introductionmentioning

confidence: 99%

Callus formation enhanced by BMP‐7 ex vivo gene therapy during distraction osteogenesis in rats

Zou

et al. 2006

Journal Orthopaedic Research

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This study was designed to observe the effects of bone morphogenetic protein-7 (BMP-7) ex vivo gene therapy on callus formation during rat mandibular distraction osteogenesis (DO). Fifty-four Sprague-Dawley rats underwent osteodistraction of the right mandible and were then randomly divided into three groups. Immediately after distraction, autologous bone marrow mesenchymal stem cells (MSCs) transfected with BMP-7, MSCs untransfected with BMP-7, and physiological saline were injected into the distraction gaps of the mandibles in groups A, B, and C, respectively. Nine animals from each group were euthanized at 2 and 6 weeks after completion of distraction. The distracted mandibles were removed and processed for radiographic, histological, immunohistochemical, and scanning electron microscopic examinations as well as Ca/P ratio analysis. Group A animals showed greater bone formation and earlier mineralization in the distracted callus when compared with group B. Similarly increased callus formation was found in group B than group C. Positive immunostaining of BMP-7 was observed in the distracted callus in all groups. However, BMP-7 expression was much stronger in group A compared with groups B and C. The results of this study suggest that BMP-7-mediated ex vivo gene transfer based on MSCs may accelerate callus formation in distraction osteogenesis and facilitate consolidation. Local gene therapy may ultimately be an alternative or supplemental approach to DO enhancement, especially for patients whose osteogenic potentials are compromised by diseases such as osteoporosis, severe trauma, and postoncologic irradiation. ß

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“…This point in time coincided with the end of active lengthening, which is characterized by the highest expression of angiogenic and osteotropic growth factors (eg, bone morphogenetic proteins, insulin-like growth factor I, and transforming growth factor β) and thus the highest rate of bone formation. [26][27][28][29][30][31] Because densitometric image analysis revealed the mean area of new bone formation in the distraction group to be more than twice the size of that in the osteotomy group 6 weeks after surgery, we expected that the delayedimage-to-region-of-interest ratio would reveal this difference. Whether the lack of increase in the region-ofinterest ratio can be attributed to a different rate of uptake of 99m Tc-HDP during intramembranous bone formation is uncertain.…”

mentioning

confidence: 99%

“…Upregulation of bone metabolism outside the lengthening zone, mediated via production of osteotropic and angiogenic growth factors during the distraction procedure, may play a role in this finding. [26][27][28][29][30][31][32] Potentially significant differences between the regions of interest may have been obscured by the sample size in the present study, but differences would be less relevant, compared with results of densitometric image analysis.…”

mentioning

confidence: 99%

Evaluation of delayed-image bone scintigraphy to assess bone formation after distraction osteogenesis in dogs

Theyse¹,

Hazewinkel²,

Terlou³

et al. 2006

ajvr

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Objective—To quantitatively assess distractioninduced bone formation in a crural lengthening model in dogs by use of delayed-image bone scintigraphy. Animals—12 mature Labrador Retrievers. Procedure—Dogs were randomly allocated to 1 of 3 groups. A circular external skeletal fixation system was mounted on the right crus of each dog. Osteotomy of the distal portion of the tibia and fibula was performed in groups 1 and 2 and was followed by a lengthening procedure of 10 mm in the first group only. The third group served as sham-operated controls. Delayed-image bone scintigraphy with technetium-99m hydroxy methylene diphosphonate was performed 2, 4, and 6 weeks after surgery. Delayedimage–to–region-of-interest, delayed-image–to–crural, and delayed-image–to–femoral scintigraphic activity ratios were calculated. New bone formation was quantified by use of densitometric image analysis, and values for the scintigraphic ratios were compared. Results—In the distraction and osteotomy groups, delayed-image–to–region-of-interest and delayedimage-to-crural ratios increased significantly. Although densitometric image analysis revealed increased bone formation after distraction, the region-of-interest ratios and crural ratios were similar in both groups. All dogs had increased delayedimage–to–femoral ratios. Conclusions and Clinical Relevance—Delayed-image bone scintigraphy ratios were not effective at differentiating between the amounts of distraction-induced bone and osteotomy-induced bone. Metabolic bone activity in the adjacent femur was increased as a consequence of circular external skeletal fixator placement. Delayed-image bone scintigraphy was not adequately sensitive to quantitatively monitor bone formation but may be useful as an early predictor of bone healing.

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Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7 during distraction osteogenesis in rabbits

Cited by 140 publications

References 21 publications

Relationships between tissue dilatation and differentiation in distraction osteogenesis

Relationships between tissue dilatation and differentiation in distraction osteogenesis

Callus formation enhanced by BMP‐7 ex vivo gene therapy during distraction osteogenesis in rats

Evaluation of delayed-image bone scintigraphy to assess bone formation after distraction osteogenesis in dogs

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