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SP0068 Osteoblasts in Bone Growth, Homeostasis and Repair
  1. C. Maes1
  1. 1Department of Development and Regeneration, KU Leuven, Leuven, Belgium


Despite the great variety of shapes and sizes, bones develop and grow through a small number of cellular mechanisms. The most common strategy, forming all the long bones of the axial (vertebrae, ribs) and appendicular skeleton (limbs), is endochondral ossification. In this process, mineralized bones form by organizing the cells and matrix of bone on scaffolding cartilage models. Absolute requirements for normal endochondral bone formation are, firstly, the provision of correctly positioned bone-forming osteoblasts and secondly, progressive neovascularization of the growing bone. We recently found that these two aspects go hand in hand. Using transgenic mouse models designed for lineage tracing of stage-selective osteogenic cells we found that specifically osteoprogenitors, and not mature osteoblasts, translocated from the perichondrium that envelopes developing bones, to initiate the ossification center inside the long bone shaft. They subsequently differentiated into mature bone-anchored osteoblasts forming trabecular bone, or remained part of the inter-trabecular immature osteogenic stroma. A similar angiogenic-osteogenic co-invasion occurred during fracture repair. Intriguingly, a subset of the osteoprogenitors that entered the developing and healing bone centers was found wrapped around the blood vessels as pericytes. This cellular interaction could possibly explain the tight spatio-temporal coupling between angiogenesis and osteogenesis that is seen in bone growth, homeostasis, repair and disease.

Therefore, in our current and future work, we focus particularly on positional aspects of osteoblast lineage cells and the interplay between these cells and their microenvironment, including interactions with the endothelial cells of the bone and marrow vasculature. Using genetically altered mice as model organism, as well as in vitro and molecular approaches, we study the mechanisms regulating these processes and their significance for bone physiology and regeneration. Elucidating the cellular and molecular mechanisms underlying the spatial control of bone formation may pave the way to new or improved anabolic therapies for widespread skeletal pathologies such as osteoporosis and impaired fracture healing.

Disclosure of Interest None Declared

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