کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5889053 | 1568133 | 2016 | 8 صفحه PDF | دانلود رایگان |
- Transcription was examined in cortical and cancellous bone separately.
- Cortical and cancellous bone have differential gene expression basally and in response to loading.
- Enhanced Wnt signaling defined the early response to loading in cortical and cancellous bone.
- Wnt upregulation persisted at a later time point in cortical, while muscle-related genes were downregulated in cancellous.
Mechanical loading is an anabolic stimulus that increases bone mass, and thus a promising method to counteract osteoporosis-related bone loss. The mechanism of this anabolism remains unclear, and needs to be established for both cortical and cancellous envelopes individually. We hypothesized that cortical and cancellous bone display different gene expression profiles at baseline and in response to mechanical loading. To test this hypothesis, the left tibiae of 10-week-old female C57Bl/6 mice were subjected to one session of axial tibial compression (9Â N, 1200Â cycles, 4Â Hz triangle waveform) and euthanized 3 and 24Â h following loading. The right limb served as the contralateral control. We performed RNA-seq on marrow-free metaphyseal samples from the cortical shell and the cancellous core to determine differential gene expression at baseline (control limb) and in response to load. Differential expression was verified with qPCR. Cortical and cancellous bone exhibited distinctly different transcriptional profiles basally and in response to mechanical loading. More genes were differentially expressed with loading at 24Â h with more genes downregulated at 24Â h than at 3Â h in both tissues. Enhanced Wnt signaling dominated the response in cortical bone at 3 and 24Â h, but in cancellous bone only at 3Â h. In cancellous bone at 24Â h many muscle-related genes were downregulated. These findings reveal key differences between cortical and cancellous genetic regulation in response to mechanical loading. Future studies at different time points and multiple loading sessions will add to our knowledge of cortical and cancellous mechanotransduction with the potential to identify new targets for mouse genetic knockout studies and drugs to treat osteoporosis.
Journal: Bone - Volume 86, May 2016, Pages 22-29