過度の繰り返し伸張刺激により機械的ダメージを受けた骨細胞が骨髄細胞の分化に与える影響

抄録

Bone is continuously subjected to repetitive loading, which leads to microdamage even if the strain level is within physiological range. The damaged site must be sensed and promptly repaired by remodeling process ; otherwise the accumulation of microdamage results in bone fracture. Osteocytes neighboring the microdamage should play an important role in detecting local mechanical environment and in initiating bone remodeling process, i. e. osteoclastic resorption, of the damaged area. The aims of this study were, therefore, to establish a relevant in vitro model for studying mechanical responses of stretched osteocytes in three-dimensional culture. We established a loading apparatus in which osteocyte-like cell line MLO-Y4 cells were three-dimensionally cultured inside collagen gel and subjected to cyclic stretching in over-physiological strain level. Excessive stretching at 10000 με damaged the gel-embedded osteocyte, resulting in significant amount of cell death. Conditioned medium obtained from the damaged osteocyte culture induced significant amount of TRACP-positive cells. It demonstrates that soluble factors secreted by the damaged osteocytes have a potential to promote osteoclastic cell formation, and further suggests that the local death of osteocytes provides an important mechanism to target remodeling to microdamaged site.