Differentiation of periodontal ligament fibroblasts into osteoblasts during socket healing after tooth extraction in the rat

Background: The entire socket after tooth extraction is filled with new bone formed by osteoblasts (Obs), but the origin of these Obs remains unknown. Thus, the proliferation and migration of paravascular and endosteal fibroblastic cells and periodontal ligament (PDL) fibroblasts (Fbs) and their differentiation into Obs during socket healing after extraction of the first maxillary molars of the rat were investigated. Methods: The proliferative activity and migration of these cells in the sockets after tooth extraction were studied using radioautography and immunohistochemistry after injection of ³H‐thymidine and 5‐bromo‐2′‐deoxy‐uridine (BrdU), respectively. Their morphological changes during differentiation was investigated by transmission electron microscopy. Results: One day after tooth extraction, PDL Fbs were the major cell type in the PDL remnant of the socket. Proliferation was low (labeling index (LI) = approximately 2%) until 16 h after tooth extraction but dramatically increased to a maximum level 1 day postextraction (LI = 23%). Between 1 and 2 days, numerous PDL Fbs in the PDL remnant actively migrated into the coagulum and continued to proliferate. On the basis of the high proliferative activity and small number of cellular organelles responsible for procollagen synthesis, these cells appear immature. At 3 days, Fbs contained more cellular organelles and deposited more collagen fibers as they replaced the coagulum with dense connective tissue and the LI declined. At 4 and 5 days, some of the Fbs began to differentiate into Obs, and the proliferation of Fbs dramatically decreased to baseline values. The migration of PDL Fbs and their differentiation into Obs were investigated by labeling with ³H‐thymidine or BrdU 1 day after tooth extraction. Heavily labeled Fbs were observed in the PDL remnant at 1 day, in the coagulum at 2 days, and in the dense connective tissue at 3 days. Labeled Obs associated with new bone were seen 4 days after injection. Endosteal and paravascular Fbs also proliferated, but at a lower level and at later time periods than the PDL Fbs. Surprisingly, endosteal and paravascular Fbs contributed only a small population of Fbs to socket healing. Conclusions: These results indicate that PDL Fbs after tooth extraction actively proliferate, migrate into the coagulum, form dense connective tissue, and differentiate into Obs which form new bone during socket healing. © 1994 Wiley‐Liss, Inc.