Abstract
Bone is an organ that is highly sensitive to changes in its mechanical loading environment. Although it is known that increased mechanical loading results in new bone formation, the cellular mechanisms underlying this response remain unclear. This investigation applied in vivo and in vitro methodologies to examine the responses of three stages of the osteoblast lineage (osteogenic colony forming unit (CFU-O), pre-osteoblast, and osteoblast) to short-term, external mechanical loads applied to the tibiae of rats. The results showed that loading protocols sufficient to induce lamellar bone formation do not affect endocortical CFU-O number or the alkaline phosphatase activity, collagen content, calcium content, or total cell number of the osteoblasts within each colony. Loading protocols sufficient to induce woven bone formation stimulated periosteal preosteoblasts to proliferate within 36 h after load application, and contribute new osteoblasts to the adaptive response within 48 h. Finally, apoptosis was suppressed during the early (1-5 d) post-load period, apparently to maintain the number of osteoblasts and pre-osteoblasts contributing to ongoing load-induced osteogenesis. These results, combined with previous examinations of post-load cellular kinetics (Turner, 1998a), indicate that the adaptive response to short-term loading involves the proliferation of pre-osteoblasts leading to the addition of new osteoblasts to the active forming surface. The recruitment of CFU-Os may be dependent on strain magnitude (which in turn determines the type of bone formed) or on the duration of loading (short-term vs. long term).