The function of the osteocyte network and its influence on the surrounding bone material
Biomaterials
Final Report Abstract
With age, the mechanosensitivity of our bones is declining with the result that physical exercise becomes less effective in stimulating bone formation. The effect is a progressing bone loss with age in healthy individuals and even more dramatic in osteoporotic patients. As a consequence, older people are more frequently afflicted by non-traumatic bone fractures. To counteract age-related bone loss, it is important to understand how bone mass is regulated, in particular in response to mechanical stimulation. Here our project contributed substantially by providing substantial evidence for the mechanism of mechanosensation in bone: the fluid flow through the lacunocanalicular network sensed by the osteocytes. Of importance is not only the obtained result, but also the used methodology. The backbone of the used methodology is advanced image technology, which includes imaging with micrometer resolution of bones in living animals, three-dimensional imaging of network structure, image analysis, spatial correlation of different images and, finally, image-informed computer modeling. We believe that this combination of obtained result and used methodology is responsible for the positive resonance to our PNAS paper in the bone research community. The paper was extensively discussed in the “What’s new”-presentation of Natalie Sims at the ECTS conference 2021 and was included in the list of the major contributions in bone research of the last year (e.g., by the Belgian Bone Club). The application of material science methods, such as x-ray scattering and micro-computed tomography, allowed to furthermore quantify the heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone. We were pleased that our research results found their way to the general public with “Der Tagesspiegel” reporting about it in its newspaper on December 16, 2020. The second important contribution concerns the interaction of the osteocyte network with the surrounding matrix. An unexpected finding was that the density of the lacunocanalicular network correlates positive with the mineral content of the bone. We concluded of this finding that somehow the LCN is also used for the storage of mineral. In quantifying this correlation by a correlation factor (corresponding to the slope in the linear relation between canalicular density and mineral content), we made another intriguing discovery. While this correlation factor was consistent within a single patient evaluating different osteons, statistically differences were found between patients. Unfortunately, no specific health data of the patients was available which allowed us to interpret the difference in a broader context of the patient’s health status. However, it is clear that the value of the correlation factor provides information of how efficient the lacunocanalicular network is involved in mineral homeostasis. In future research we aim at a more concrete interpretation of this new bone parameter.
Publications
- (2019). The contribution of the pericanalicular matrix to mineral content in human osteonal bone. Bone, 123, 76-85
Roschger, A., Roschger, P., Wagermaier, W., Chen, J., Van Tol, A. F., Repp, F., ... & Weinkamer, R.
(See online at https://doi.org/10.1016/j.bone.2019.03.018) - (2020). Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone. Journal of structural biology, 212(2), 107616
Schemenz, V., Gjardy, A., Chamasemani, F. F., Roschger, A., Roschger, P.,..., Weinkamer, R., ... & Wagermaier, W.
(See online at https://doi.org/10.1016/j.jsb.2020.107616) - (2020). Network architecture strongly influences the fluid flow pattern through the lacunocanalicular network in human osteons. Biomechanics and modeling in mechanobiology, 19(3), 823-840
van Tol, A. F., Roschger, A., Repp, F., Chen, J., Roschger, P., Berzlanovich, A., ... & Weinkamer, R.
(See online at https://doi.org/10.1007/s10237-019-01250-1) - (2020). The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture. Proceedings of the National Academy of Sciences, 117(51), 32251-32259
van Tol, A. F., Schemenz, V., Wagermaier, W., Roschger, A., Razi, H., Vitienes, I., ... & Weinkamer, R.
(See online at https://doi.org/10.1073/pnas.2011504117) - (2021). Function of the Osteocyte Lacunocanalicular Network in Bone Mechanoresponsiveness. Doctoral thesis, Humboldt University of Berlin
van Tol, A.
(See online at https://doi.org/10.18452/22768)
