RECRUITMENT AND PROLIFERATIVE RESPONSES OF OSTEOBLASTS AFTER MECHANICAL LOADING IN-VIVO DETERMINED USING SUSTAINED-RELEASE BROMODEOXYURIDINE

Mechanical bending of a rat's tibia in vivo can increase endocortical bone formation by over sixfold, It has been proposed that mechanical l oading increases bone formation by driving osteoprogenitor cells in th e marrow stroma to progress through the cell cycle and subsequently di fferentiate into osteoblasts at the cortical bone surfaces. We used a sustained-release preparation of 5-bromo-2'-deoxyuridine (SR-BrdUrd) t o determine the origin of endocortical osteoblasts in rat tibiae after mechanical loading. SR-BrdUrd was bioavailable for the entire 96 h du ration of the experiments, so all cells that progressed through a cell cycle were labeled with BrdUrd, Although the endocortical osteoblast surface was significantly increased (p < 0.05) at 48 h after loading, the percentage of BrdUrd-labeled osteoblasts did not increase, suggest ing that the newly differentiated osteoblasts on the endocortical surf ace did not originate from proliferating cells. At 96 h after loading, 30-40% of the endocortical osteoblasts were BrdUrd labeled. The major ity of BrdUrd-labeled osteoblasts appeared on the endocortical bone su rface within the third day after loading, indicating that proliferatio n and differentiation of precursors in:to endocortical osteoblasts req uired 72 h after the loading stimulus. These results indicate that mec hanical loading can cause two distinct osteoblastic responses: an imme diate response within 48 h in which osteoblasts are recruited from non dividing preosteoblasts and/or bone-lining cells, and a delayed respon se involving proliferation and differentiation of preosteoblasts that requires greater than or equal to 3 days. (C) 1998 by Elsevier Science Inc. All rights reserved.