Impact of conditional Piezo1 knockout on loaded and unloaded cranial bone quality

Introduction: Bone remodeling is a major topic in medical bone research. It is consensus that bone remodeling is a mechanosensitive process that is orchestrated by bone cells called osteocytes. Here, ion channels called Piezo1 are a promising candidate as the main mechanosensitive proteins enabling mechanical responsiveness of osteocytes.Since mechanosensation is known to be a main driver of bone quality, we hypothesize that bones with a Piezo1 knockout have a lower bone quality than controls, if loaded. Additionally, we hypothesize that unloaded bone of the same skeletal region will not be affected in case of a Piezo1 knockout. Bone quality shifts are expected to be reduced thickness, increased porosity and lower tissue mineral density. Because both, loaded and unloaded bone, are present in the same anatomical region we chose to investigate cranial bone of mice. Here, temporal bone is loaded by muscles during chewing, while parietal bone is unloaded due to the absence of muscle attachments. Both regions are formed through intramembranous ossification.

Methods: Mouse skulls (Piezo1 ^Dmp1Cre and wildtype) were analyzed using high-resolution μCT-imaging at an isometric voxelsize of 10 μm. One volume of interest (VOI) is located in the parietal bone and another in the loaded temporal bone. Furthermore, both regions were compared to the femur of the mice to differentiate locomotive bone from skull bone. Bone quality was assessed in terms of bone thickness and porosity, as well as bone mineral density (BMD) and tissue mineral density (TMD).

Results: We found that specifically temporal bone differed significantly between control and knockout, while parietal bone did not differ. The thickness of temporal bone was significantly lower in knockout. Furthermore, the tissue mineral density of loaded bone is significantly higher in the control group compared to the Piezo1 ^Dmp1Cre knockout. These results correspond to the femoral results with a reduced cortical thickness in knockout.

Discussion: The results are in line with results for the locomotive skeleton. Additionally, we have shown that the unloaded parietal bone is not affected by the Piezo1 ^Dmp1Cre knockout, while the loaded temporal bone significantly declines in bone quality. Therefore, unloading (parietal bone) is equally effective as Piezo1 knockout (temporal bone) to reduce bone quality. Furthermore, temporal bone appears to be more affected by Piezo1 ^Dmp1Cre knockout compared to the femur. These findings raise the question of what additional mechanisms regulate bone remodeling in the parietal bone and suggest testing for parietal bone response to mechanical loading.

Keywords: Piezo1, Osteocytes, Bone quality, Loading, Skull

Korrespondenzadresse: Felix Nikolai von Brackel, Universitätsklinikum Hamburg-Eppendorf, Institut für Osteologie und Biomechanik, Lottestraße 55a, 22529 Hamburg, Deutschland, E-Mail: [e-mail]

Publication History

Article published online:
21 March 2025