anti-VEGF neutralizing antibody inhibits the progress of ossification of the ligament in the ossification of the spinal ligament

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Tiptoe Walking (ttw) mouse is a model for ectopic ossification of various soft tissues in the extremities and spine. Ectopic ossification of spinal ligaments results in ossification of the posterior longitudinal ligament (OPLL) and of the yellow ligament (OYL) of the spine. In this study, anti-VEGF neutralizing antibody was administered intraperitoneally in ttw mouse and the ossified area of the spinal ligament was measured. The increase of the ossification of the spinal ligament was inhibited in the ttw mouse, which anti-VEGF neutralizing antibody was administered (group V), compared with the control ttw mouse, which PBS was administerd (group P). Osteocalcin immunopositive cells and expression of type X collagen were observed in the ossification front of group P, whereas safranine-O staining cells was seen and expression of type X collagen were little in that of group V, which indicates that hypertrophy of the chondrocytes and/or induction of the osteoblasts are inhibited and chondrocytes are persisted. It suggests that suppression of VEGF may inhibit the course of endochondral ossification in the spinal ligament. Vascular invasion was suppressed in the ossified area of the spinal ligament in group V compared with that in group P, which suggested that inhibition of vascular invasion by administration of anti-VEGF neutralizing antibody may also suppress the endochondral ossification in the spinal ligament.