Bone remodelling maintains the functionality of skeletal tissue by locally
coordinating bone-resorbing cells (osteoclasts) and bone-forming cells
(osteoblasts) in the form of Bone Multicellular Units (BMUs). Understanding the
emergence of such structured units out of the complex network of biochemical
interactions between bone cells is essential to extend our fundamental
knowledge of normal bone physiology and its disorders. To this end, we propose
a spatio-temporal continuum model that integrates some of the most important
interaction pathways currently known to exist between cells of the osteoblastic
and osteoclastic lineage. This mathematical model allows us to test the
significance and completeness of these pathways based on their ability to
reproduce the spatio-temporal dynamics of individual BMUs. We show that under
suitable conditions, the experimentally-observed structured cell distribution
of cortical BMUs is retrieved. The proposed model admits travelling-wave-like
solutions for the cell densities with tightly organised profiles, corresponding
to the progression of a single remodelling BMU. The shapes of these spatial
profiles within the travelling structure can be linked to the intrinsic
parameters of the model such as differentiation and apoptosis rates for bone
cells. In addition to the cell distribution, the spatial distribution of
regulatory factors can also be calculated. This provides new insights on how
different regulatory factors exert their action on bone cells leading to
cellular spatial and temporal segregation, and functional coordination.Comment: 14 pages, 5 figures; v2: Completed model description after Eq. (16),
clarified discussion/description after Eq. (23), between Eqs. (29)-(31), and
in 2nd bullet point in conclusion