Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling

Kimberly A. Jacobsen; Zainab S Al-Aql; Chao Wan; Jennifer L. Fitch; Stephanie Stapleton; Zachary Mason; Robert Cole; Shawn R. Gilbert; Thomas L. Clemens; Elise F. Morgan; Thomas A. Einhorn; Louis C. Gerstenfeld

doi:10.1359/jbmr.080103

February 5, 2008Journal of Bone and Mineral ResearchOpen Access

Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling

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Key Points

To investigate whether new bone formation during distraction osteogenesis depends on vascularization mediated by VEGFR1 and VEGFR2 signaling pathways.
Targeted antibody blockade was administered to inhibit both VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or VEGFR2 alone in a murine tibia distraction osteogenesis model.
Vessel architecture, bone formation, and skeletal cell lineage progression were evaluated using micro-computed tomography and molecular expression analyses.
Micro-computed tomography demonstrated a significant decrease in bone formation following dual VEGFR1 and VEGFR2 blockade, with a smaller reduction observed after single VEGFR2 blockade.
Vessel volume, vessel number, and vessel connectivity showed progressive and significant inhibition across single- and dual-receptor blockade groups.
Single VEGFR2 inhibition triggered selective early chondrogenesis, whereas dual VEGFR1 and VEGFR2 blockade resulted in complete failure of both osteogenesis and chondrogenesis.

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Implication

Experimental study shows VEGFR1 and VEGFR2 blockade impairs vascularization and bone formation in mice, indicating both receptors are necessary to direct osteogenesis over cartilage formation.

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Jacobsen et al. (2008) studied this question.

synapsesocial.com/papers/6a738bad644e61a44f4e65b8 https://doi.org/10.1359/jbmr.080103

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Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling

Key Points

No abstract yet

Implication

Discussion

Cite This Study

Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling

Key Points

No abstract yet

Implication

Discussion

Cite This Study

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