Examining the role of the osteocyte lacunocanalicular network architecture in craniosynostosis
Taylor deVet 1,2, Aren Bezdijan2, Maximillian Rummler3, Markus Hartmann4, Stephane Blouin4, Nadja Fratzl-Zelman4, Roy Dudley5, Richard Weinkamer3, Bettina Willie1,2
1 UU直播, 2 Shriners Hospital for Children,聽3 Max Planck Institute of Colloids and Interfaces, 4 Ludwig Boltzmann Institute of Osteology, 5 Montreal Childrens Hospital
Bone adapts to changes in the mechanical environment through sensation of fluid flow in the bone matrix. Osteocytes, the lacunae they inhabit, and the canaliculi are called the osteocyte-lacunar-canalicular network (OLCN). The OLCN changes as the bone ages, altering the shape and size of the osteocytes and the connectivity of canaliculi. Altered connectivity changes fluid flow throughout the OLCN, which affects the way the mechanical environment is sensed by osteocytes. Normal skull growth progresses due to pressure from the growing brain, keeping suture gaps patent to allow for expansion. Craniosynostosis is a disorder whereby the skull sutures fuse prematurely, causing problems with skull and brain growth. Although craniosynostosis has been associated with many genes, there are a substantial number of non-syndromic cases. Thus, the aim of this study was to investigate the OLCN surrounding and interacting with the suture in non-syndromic cases. We hypothesized that the OLCN architecture is altered near the bonesuture interface in a suture-patency dependent manner. Craniosynostosis samples have been collected from 20 donors undergoing neurosurgeries at the MUHC. Samples were imaged using microCT to assess BMD and microstructure. Samples were then stained with rhodamine and imaged using confocal microscopy for OLCN mapping. Samples were also imaged using second harmonic generation for collagen mapping. QBEI was performed to measure mineral content. Synchrotron radiation imaging was then performed at the SOLEIL Synchrotron facility to characterize the vascular and lacunar porosity at the interface of the bone and suture. Bone directly interfacing with the suture had a higher calcium content than older bone that had been remodelled. Bone at the suture interface had a rougher surface, indicative of resorption activity, where it interacted with the fibrous tissue of the surface. The osteocytes in this region were larger and less organized than that in lower density, secondary bone. Collagen was more organized in remodelled bone than in primary bone, with the tissue in the suture having collagen in a very different texture than that in the bone. Analysis is ongoing to quantify the lacunar and OLCN properties in primary and secondary bone, identified by QBEI. The correlation of these techniques allows for an in depth understanding of how OLCN architecture influences premature suture fusion occurring in these craniosynostosis patients from a structural and materials point of view.