Computational model of cell cell interaction in bone remodelling

Müller, Felix Johannes and Haack, Fiete and Köster, Till and Uhrmacher, Adelinde M. (2024) Computational model of cell cell interaction in bone remodelling. In: ELAINE 2024, 20-22 Mar 2024, Rostock, Germany. Poster.

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Introduction: Adult bone remodeling is a constantly occurring, balanced process of bone erosion and formation driven by the coordinated action of bone resorbing cells (osteoclasts) and osteoid-forming cells (osteoblasts). While global, hormonal regulation between cell types is well understood, detailed knowledge about the exact spatio-temporal processes that lead to the initiation, formation and maintenance of bone remodelling unit is lacking. Here we present a computational model that provides a comprehensive representation of the cellular interaction during the formation of the resorption pit. Methods: The model is implemented in the rule-based multi-level modeling language ML-Rules 3, which allows for modeling and simulation of intra- and intercellular processes using dynamic compartments. While signaling molecules are considered on a population level, layered bone structures such as bone matrix, bone surface and bone marrow envelope and corresponding cells types, such as osteoclasts and osteoblasts are represented as individual, nested and dynamic compartments. Results: Various important processes on the cellular level during bone remodelling are explored in the model. The model emphasizes the crucial role of direct cell-cell contact during the recruitment and migration of pre-osteoclasts to the bone surface through the bone marrow envelope and bone surface cell layers as well as its promoting effect on their differentiation and fusion into multinucleated osteoclasts. Further the model highlights the impact of the RANK/RANKL/OPG pathway in terms of mRANKL availability, OPG diffusion, and boundary conditions on the migration, resorption and apoptosis of osteoclasts; and on the proliferation and activation of (pre-)osteoblasts. Conclusion: Our spatio-temporal model of adult bone remodeling highlights key regulatory elements of bone cell interaction in the spatial and biochemical environment of the resorption cavity. It serves as a control model for relevant cell-biological processes of bone remodeling and eventually provides means to study implications and potential effects of electrical or mechanical stimulation.

Item Type: Conference or Workshop Item (Poster)
Projects: MaCE