Mathematical modelling of basic multicellular units: the functional units of bone remodeling

Pascal Buenzli, Peter Pivonka

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Abstract

Bone remodeling denotes the continual renewal of the bone matrix over our lifetime. This renewal is operated by self-contained groups of bone-resorbing cells called osteoclasts and bone-forming cells called osteoblasts. These functional groups of cells ensure the tight coordination between bone resorption and bone formation required for skeletal maintenance and mineral homeostasis. Many bone disorders such as osteoporosis and osteopetrosis are associated with a deregulation of the balance between resorption and formation within basic multicellular units (BMUs). While usually recognized as the basic functional unit of bone remodeling, BMUs are still incompletely understood. Coupling between osteoclasts and osteoblasts is known to occur through several signaling molecules such as the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), transforming growth factor beta (TGFβ), and parathyroid hormone (PTH). However, the mechanisms of action of these molecules between spatially segregated populations of osteoclasts and osteoblasts within BMUs are unclear. How a BMU initiates and progresses through bone and terminates and how these events translate to cell distribution and cellular interactions is also unclear. To shed light on the spatio-temporal dynamics of BMUs and the complex interactions of their constituents, several computational models describing BMU behavior have been developed in recent years. These modeling efforts have focused on different aspects of BMU regulation including (i) chemotactic effects of RANKL signaling in trabecular BMUs [1,2]; (ii) timing of RANKL and OPG signaling in trabecular BMUs [3]; (iii) cellular organization in cortical BMUs owing to biochemical pathways [4]; (iv) stages of the BMU’s life, initiation, and progression stages—implications for tetracycline-based assessment of matrix apposition rates [5]; (v) formation of the resorption cavity and osteoclast resorption pattern [1,2]; (vi) refilling of the resorption cavity and osteoblast secretory activity [5,6]; (vii) repair of microdamage in the bone matrix and biomechanical steering of BMU progression [7]; and (viii) mechanical feedback in trabecular BMUs [8]. The objective of this book chapter is to give an overview of the state-of-the-art computational models of BMUs and their application to bone remodeling with a special emphasis on model developments from our own research.
Original languageEnglish
Title of host publicationComputational Bioengineering
EditorsGuigen Zhang
Place of PublicationBoca Raton FL USA
PublisherTaylor & Francis
Pages45-74
Number of pages30
ISBN (Print)9781466517561
DOIs
Publication statusPublished - 2015

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