Strains Guide Osteoclasts Across Bone Trabeculae

Strains Guide Osteoclasts Across Bone Trabeculae

STRAINS GUIDE OSTEOCLASTS ACROSS BONE TRABECULAE René van Oers, Bert van Rietbergen, Peter Hilbers, Keita Ito, Rik Huiskes Introduction An osteoclast is placed at the side of a single strabecula Trabecular bone is porous, a lattice of bony struts called (Fig.2, left). The top and bottom end of the trabecula are trabeculae, which are aligned to the dominant load covered by plates (not shown) on which extrenal loads are direction. Bone is remodeled by resorbing osteoclasts and placed. In one series of 5 simulations the trabecula is forming osteoblasts. Osteoclasts dig a trench over the subjected to a tensile load. In 5 other simulations the trabecular surface, closely followed by osteoblasts that fill it with new bone (Fig.1). trabecula remains unloaded. Results In the loaded simulation, the osteoclast meanders along the surface (Fig.2, middle) since its resorption depth is limited by strain-induced inhibiting signals that are strongest at the bottom of the trench. When the trabecula is not loaded, resorption is random (Fig.2, right), and likely to perforate the trabecula. Figure 1: Remodeling of trabecular bone It is unknown why osteoclasts resorb along the surface and do not perforate the trabecula. Smit and Burger [1] performed a finite element analysis of a trabecula with a resorption lacuna. They found that strains were highest at the bottom of the lacuna. We hypothesize that these strains induce osteocytes (cells within the bone) to secrete osteoclast-inhibiting signals, thus restricting osteoclastic resorption to the trabecular surface and preventing perforation. Here, we investigate this hypothesis in a Figure 1: An osteoclast (red) starts at the side of a trabecula. When the trabecula is loaded, the osteoclast digs a trench (red path) along its computational model. side. In the absence of loading, the osteoclast digs randomly, thereby perforating the trabecula. Methods Earlier, we developed a finite-element based bone Discussion adaptation model [2], that produces trabecular-like These results demonstrate that the typical surface architectures. Depending on the local strain-energy-density resorption of osteoclasts can indeed be explained by osteocytes send signals to the bone surface, where they mechanical factors. control the activity of osteoclasts and osteoblasts. Osteoclastic resorption was represented as cavities References [1] Smit & Burger (2000). J Bone Miner Res 15:301. occurring along the bone surface. For the present work [2] Huiskes et al. (2000). Nature 405:704. osteoclasts are explicitly represented with a cell simulation [3] Glazier & Graner (1993). Phys Rev E 47:2128. model [3], which allows us to investigate how the proposed [4] van Oers et al. (2008). Bone 42:250. strain-based signals guide resorbing osteoclasts. / Biomedical Engineering.

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