Hyperplasia and accelerated hypertrophy of marrow adipocytes with knee immobilization were sustained despite remobilization

Skeletal disuse can cause an accumulation of bone marrow adipose tissue (MAT) characterized by a combination of marrow adipocyte hyperplasia and/or hypertrophy. The malleability of MAT accumulation and of the hyperplasia and hypertrophy upon remobilization is unknown. In this study, we showed extensive hyperplasia and accelerated hypertrophy of bone marrow adipocytes in the proximal tibia epiphysis of rat knees immobilized for durations between 1 and 32 wk. Similar histomorphometric measures of adipocytes carried out in unoperated controls allowed distinguishing the effects of immobilization from the effects of aging. Although both knee immobilization and aging led to adipocyte hypertrophy, adipocyte hyperplasia was the hallmark signature effect of immobilization on MAT. Both bone marrow adipocyte hyperplasia and hypertrophy were sustained despite knee remobilization for durations up to four times the duration of immobilization. These results suggest that adipocyte hyperplasia is the predominant mechanism explaining MAT accumulation in skeletal disuse. In this model, the changes were unremitting for the investigated time points. Investigating the cellular and molecular mechanisms of marrow adipocyte mechanoregulation will be important to better understand how adipocytes adapt to changes in mechanical environments.