99mTC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

摘要

^99mTc-Methylene diphosphonate (^99mTc-MDP) is widely used in clinical settings to detect bone abnormalities. However, the mechanism of ^99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography (gamma scintigraphy or SPECT), ex vivo micro-computed tomography, and histology to monitor ^99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with ^99mTc-MDP at different time points, and quantitated for ^99mTc-MDP uptake with a gamma counter. We demonstrated that ^99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The ^99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. ^99mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that ^99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for ^99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.