Upregulation of matrix metalloproteinase (MMP)‐1 and its activator MMP‐3 of human osteoblast by uniaxial cyclic stimulation

Abstract

Proper mechanical loading is essential for bone remodeling and maintenance of human skeletal system. Matrix metalloproteinases (MMPs) are secreted by mesenchymal stromal lining cells and osteoblasts to prepare the initiation sites for osteoclastic bone resorption at the beginning of the remodeling cycle. However, only a few studies have addressed the effect of mechanical stress on MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) in osteoblasts. In this study, the response of human osteoblasts to uniaxial cyclic stretching was investigated to clarify this more in detail. Stretching affected the orientation of the osteoblasts, and quantitative reverse transcription-polymerase chain reaction revealed coordinated upregulation of MMP-1 and its activator MMP-3 mRNA by cyclic 5% stretching at 3 h (p < 0.01). Upregulation of cyclooxygenase-2 mRNA was also found in response to cyclic 1 and 5% stretchings at 1, 3, and 6 h (p < 0.01). No changes were found in MMP-2, TIMP-1, and -2. The mRNA expression of MMP-9 was low and MMP-13 was not detected. This study suggests that MMP-1 and -3, enhanced by uniaxial cyclic mechanical stimulation of osteoblasts, are candidate key enzymes in the processing of collagen on bone surface, which might be necessary to allow osteoclastic recruitment leading to bone resorption. The strain might also play a role in cleaning of demineralized bone surface during the reversal phase, before bone formation starts.