Non-resorbing osteoclasts induce migration and osteogenic differentiation of mesenchymal stem cells

Osteoclast activity has traditionally been regarded as restricted to bone resorption but there is some evidence that also non-resorbing osteoclasts might influence osteoblast activity. The aim of the present study was to further investigate the hypothesis of an anabolic function of non-resorbing osteoclasts by investigating their capability to recruit mesenchymal stem cells (MSC) and to provoke their differentiation toward the osteogenic lineage. Bone-marrow-derived human MSC were exposed to conditioned media (CM) derived from non-resorbing osteoclast cultures, which were generated from human peripheral blood monocytes. Osteogenic marker genes (transcription factor Runx2, bone sialoprotein, alkaline phosphatase (AP), and osteopontin) were significantly increased. Osteogenic differentiation (OD) was also proved by von Kossa and AP staining occurred in the same range as in MSC cultures stimulated with osteogenic supplements. Chemotactic responses of MSC were measured with a modified Boyden chamber assay. CM from osteoclast cultures induced a strong migratory response in MSC, which was greatly reduced in the presence of an anti-human platelet-derived growth factor (PDGF) receptor beta antibody. Correspondingly, significantly increased PDGF-BB concentrations were measured in the CM using a PDGF-BB immunoassay. CM derived from mononuclear cell cultures did not provoke MSC differentiation and had a significantly lower migratory effect on MSC suggesting that the effects were specifically mediated by osteoclasts. In conclusion, it can be suggested that human non-resorbing osteoclasts induce migration and OD of MSC. While effects on MSC migration might be mainly due to PDGF-BB, the factors inducing OD remain to be elucidated.