Mechanical loading prevents decreased bone formation responses of osteoblasts by a bone morphogenic protein‐dependent mechanism

Abstract

Bone loss due to osteoporosis, disuse, and microgravity is a significant health problem. A low magnitude and high frequency (LMHF) mechanical loading has been shown to prevent bone loss in animals and humans. However, the underlying mechanisms and the target cells through which LMHF loading alleviates bone loss are not known. We hypothesized that direct application of LMHF loading to osteoblasts alters cell response, preventing decreased bone formation induced by disuse. To test our hypothesis, pre‐osteoblast 2T3 cells were exposed to the Random Positioning Machine (RPM) and intervened with LMHF loading (0.3g, 30Hz, 10 min). The RPM decreased bone formation markers as determined by alkaline phosphatase (ALP) activity and mineralization even in the presence of BMP4 (20ng/ml). However, LMHF loading prevented the RPM‐induced decrease in both markers. Mineralization induced by LMHF loading was enhanced by treatment with BMP4 and blocked by the BMP antagonist noggin, suggesting a role for BMPs. LMHF loading also rescued the RPM‐induced decrease in ALP, runx2, osteomodulin, parathyroid hormone receptor 1, and osteoglycin. These findings show that osteoblasts respond directly to LMHF loading, providing mechanistic insight into how LMHF loading prevented bone loss in vivo. The genes identified here provide potential targets for pharmaceutical treatments that may be used with LMHF loading to better treat bone loss.