Effects of Mechanical Loading on Cranial Joint Mesenchymal Stem Cell Proliferation

Sutures are the primary sites of cranial bone growth, allowing the skull to accommodate the growing brain. External mechanical stimulus has been shown to delay suture fusion and induce tissue remodelling. Recent studies suggest that in vivo cyclic bone loading increased proliferation of mesenchymal stem cells (MSC) in the coronal suture. The overall aim of this study was to understand how many loading sessions (exposure-response) and how long after loading (time-course) did MSC proliferation increase in the coronal suture. In the exposure-response analysis, mice underwent 1, 3, or 5 loading sessions between Postnatal day 7 (P7) and P11, and in the time-course analysis, treated mice underwent 10 loading sessions between P7 and P21. Loading sessions were 10 minutes at a frequency of 1 Hz and a force of 10 g (0.1 N). The loading tip was positioned on the posterior aspect of the left frontal bone, dorsal to the coronal suture. The EdU marker shows a statistically significant increase in proliferation after one loading session and a decrease after three loading sessions. The PCNA marker shows a statistically significant increase after three and five loading sessions. The exposure-response analysis showed that when the results of both markers are combined, levels of proliferation cannot be interpreted until at least five loading sessions have been completed, after which a clear increase in proliferation was observed. In the time-course analysis, proliferation was highest immediately after the final treatment session and 24 hours after the final loading session the effects of mechanical bone loading gradually returned to baseline.