We examined the role of Tie2 in regulating wound healing after tooth extraction. Wistar rats underwent maxillary incisor tooth extraction, and immunodetection techniques were used to determine Tie2 expression in the healing wound. The wound was initially filled with blood coagulum containing densely aggregated erythrocytes, leukocytes, fibrin, and endothelial progenitor cells, indicating that blood vessel formation started in the socket. Tie2 was detected on monocytic cell membranes. On day 3, fibroblastic cells proliferated in the coagulum, small vessels appeared by day 5, and new bone formed in the vessel-rich area. Robust woven bone trabeculae were present around vessels by day 7, and woven bone and osteoclast-like giant cells were present on day 10. Woven bone surrounded sinusoidal capillarylike vessels. Full-length (140-160 kDa) Tie2 was not detected at any time, although Tie2 fragments were present in the healing wound. N-terminus- and C-terminus-specific Tie2 antibodies detected 40-kDa and 60-kDa fragments or 70-kDa and 50-kDa fragments, respectively. The levels of these fragments decreased during the first 3 days and started to increase by day 5-10. The Tie2 extracellular domain initially inhibited angiogenesis, and its degradation relieved inhibition of new vessel formation. The onset of vessel formation in the wound may be induced by scattered endothelial progenitor cells.
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