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.

Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity

“…This controversy can be due to species differences (human vs. rat), or can probably indicate different mechanisms in scoliosis and in disc degeneration disease. A positive effect of mechanical forces on MMP-1 expression or secretion has been reported also in various other models, from periodontal tissues to osteoblastic cells [30-32]. The increase of MMP-1 expression observed in this study seems to be dependent on the intensity of deformation and on the site of the tissue affected, as convex areas are more affected compared to concave ones.…”

Osteoactivin Promotes Breast Cancer Metastasis to Bone

“…Moreover, osteoactivinexpressing 66cl4 cells flushed directly from osteolytic bone lesions retain high levels of osteoactivin and MMP-3 transcripts. Interestingly, studies have linked increased MMP-3 expression in osteoblasts under conditions associated with enhanced bone resorption, such as cytokine stimulation (41), estrogen withdrawal (42), or mechanical loading (43). The ability of osteoactivin to induce MMP-3 expression in breast cancer cells may be particularly relevant with respect to their ability to metastasize to bone.…”

Collagen Type I as a Ligand for Receptor-Mediated Signaling

“…Osteoblasts have been demonstrated to produce MMP-1, which may affect their differentiation [114]. In addition, MMP-1 was shown to be upregulated in response to mechanical loading [115]. However, it is not clear if MMP-1 activity toward collagen type I is important for osteoblasts.…”