The function of the osteocyte network and its influence on the surrounding bone material

• Applicants: Wolfgang Wagermaier, Ph.D.; Dr. Richard Weinkamer
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Biomaterials
• Term: from 2015 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 272944896

Bone consists of mineralized tissue, representing a nanostructured organic-inorganic composite material, and cells (osteocytes) distributed in a network-like porous space, the osteocyte lacunar canalicular network (OLCN). Osteocytes are thought to sense mechanical stimuli and, therefore, act as control center for bone renewal (remodeling) and bone adaptation. In addition, evidence increases that osteocytes can actively change the mineral content of the surrounding bone. This process may contribute to mineral homeostasis and change the mechanical properties of bone.Only since recently, the reaction of bone to a controlled mechanical stimulus can be monitored by multiple imaging. In these samples both the mechanical stimulation and the recent history of remodeling events is known. Over the last years, we have developed methods to image and quantify the OLCN in bone and have a long term experience in characterizing the organic and inorganic phases of bone using X-ray scattering and Raman spectroscopy. Applying these technological advances to bone samples of known structural changes, we want to test the hypothesis, if the osteocyte network acts as a mechanosensing system as well as a transport system during (de)mineralization processes. To test this hypothesis we first characterize in the same bone sample the organization of the cellular component (i.e., the structure of the OLCN) and the material component (i.e., the mineral particles and organic collagen matrix) and then analyze spatial correlations between them. Our specific aims are: 1) To find evidence that the OLCN adapts its topology to local mechanical strains. 2) To detect influences of the OLCN on characteristics of the bone material, in particular, in the vicinity of remodeling sites. 3) To correlate transport-parameters from the OLCN with remodeling and mineralization patterns 4) To quantify bone mineral quality and OLCN topology in regions with distinct order of tissue organization. To tackle the last objective, we study as a second model system bone healing in a mouse femur. During healing a so-called fracture callus is formed rapidly with different order of tissue organization. Since the temporal course of the callus formation is known this model system allows a closer look at the formation of the OLCN and its interaction with the surrounding material.Our approach for this project is that a pure biological analysis of osteocytes and their communication with other cells is insufficient for an understanding of their role for bone health. Our materials science viewpoint will contribute to a clarification of the interaction of the OLCN with the surrounding environment in bones where the recent structural changes (remodeling, healing) are known.

• DFG Programme: Research Grants