Trabecular bone turnover and bone marrow cell development in tail-suspended mice

To clarify the relationship between the changes of trabecular bone turnover and bone marrow cell development during mechanical unloading and reloading , we performed experiments with tail-suspended mice. At 8 weeks of age, 150 male ddY mice were divided into three body weight-matched groups. Mice of group 1 were euthanized at the start of tail suspension (day 0) as a baseli ne control, The mice of group 2 were subjected to hindlimb unloading by tai l suspension for 14 days and reloading for the subsequent 14 days. The mice of group 3 were normally loaded as age-matched controls. Mice of groups 2 and 3 were sacrificed at 7, 14, and 28 days after the start of the experime nt. In the first experiment (histomorphometric study of tibiae), unloading for 7 and 14 days and reloading for the subsequent 14 days significantly de creased the bone volume compared with that in the age-matched controls, res pectively. Unloading for 7 and 14-days also significantly reduced the bone formation rate (BFR/BS), respectively, but reloading for the subsequent 14 days restored BFR/BS to the control level. While the unloading for 7 and 14 days significantly increased both the osteoclast surface (Oc.S/BS) and the osteoclast number (Oc.N/BS), the reloading for the subsequent 14 days decr eased Oc.S/BS and Oc.N/BS, respectively. In the second experiment (bone mar row cell culture study of tibiae), unloading for 7 and 14 days reduced the adherent stromal cell number, without significance. Unloading for 7 days si gnificantly decreased the mineralized nodule formation. Reloading for the s ubsequent 14 days markedly increased the adherent stromal cell number and t he mineralized nodule formation. Unloading for 7 days significantly increas ed the number of tartrate-resistant acid phosphatase (TRAP)-positive multin ucleated cells, These data clearly demonstrate that unloading reduces bone formation and increases bone resorption, and subsequent reloading restores reduced bone formation and suppresses increased bone resorption, closely as sociated,vith the changes in adherent stromal cell number, mineralized nodu le formation, and the number of TRAP-positive multinucleated cells.