A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently

Biochemical and Biophysical Research Communications
Pia Rosgaard JensenJean-Marie Delaissé

Abstract

The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This...Continue Reading

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Citations

Feb 11, 2016·Histochemistry and Cell Biology·Mohamed Essameldin AbdelgawadThomas Levin Andersen
Feb 26, 2014·Current Opinion in Pharmacology·Gudrun Stenbeck, Fraser P Coxon
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Sep 26, 2019·Annual Review of Physiology·Natalie A Sims, T John Martin
Jan 20, 2021·Bone·Pia Rosgaard JensenJean-Marie Delaisse

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