Catabolic activity of osteoblast lineage cells contributes to osteoclastic bone resorption in vitro

Osteoblast lineage cells in human bone were recently shown to colonize eroded bone surfaces and to closely interact with osteoclasts. They proved to be identical to reversal cells and are believed to differentiate into bone-forming osteoblasts thereby coupling resorption and formation. However, they also exert catabolic activity that contributes to osteoclastic bone resorption, but this has not received much attention. Herein, we used co-cultures of primary human osteoblast lineage cells and human osteoclasts derived from peripheral blood monocytes to investigate whether a catabolic activity of osteoblast lineage cells could impact on osteoclastic bone resorption. Through a combination of immunofluorescence, in situ hybridization and time-lapse experiments, we show that MMP-13expressing osteoblast lineage cells are attracted to and closely interact with bone-resorbing osteoclasts. This close interaction results in a strong and significant increase in the bone resorptive activity of osteoclasts – especially those making trenches. Importantly, we show that osteoclastic bone resorption becomes sensitive to inhibition of matrix metalloproteinases in the presence, but not in the absence, of osteoblast lineage cells. We propose that this may be due to the direct action of osteoblast-lineage-derived MMP-13 on bone resorption.