ALENDRONATE REDUCES ADHESION OF HUMAN OSTEOCLAST-LIKE CELLS TO BONE AND BONE PROTEIN-COATED SURFACES

Bisphosphonates (BPs) an potent inhibitors of bone resorption and are therapeutically effective in disease of increased bone turnover, but t heir mechanism(s) of action remain to be elucidated. Using as experime ntal model human osteoclast-like cell lines derived from giant cell tu mors of bone, extensively characterized for their osteoclast features, we investigated the adhesive properties of osteoclasts on bone slices and on different proteins of the extracellular matrix in the presence of BPs. Adhesion assays using bone slices pretreated with ALN, at the established active concentration, showed that, although the morpholog y of osteoclasts plated onto pretreated bone slices was not modified, the number of adherent cells was reduced by the treatment of about 50% vs. controls. The effect of ALN on the adhesion of osteoclast-like ce lls onto specific extracellular matrix proteins, such as bone sialopro tein-derived peptide, containing the RGD sequence, conjugated to BSA ( BSP-BSA) and fibronectin (FN), was also tested. In the case of FN the treatment with ALN of protein-coated wells did not modify the percenta ge of cell adhesion compared with the control, whereas onto BSP-BSA th e presence of ALN significantly reduced adhesion of about 40-45%, sugg esting that the inhibitory effect of ALN on cell adhesion could probab ly be due to the interference with receptors specifically recognizing bone matrix proteins as alpha(v)beta(3) integrins. Furthermore, ALN in duced Ca-mediated intracellular signals in osteoclasts, triggering a 2 -fold increase in intracellular calcium concentration.