Prostate caner is a common disease in western countries. Primary prostate tumors preferentially disseminate to bones. Homing and activity of cancer cells in the bone microenvironment as well as specific mechanisms used by tumor cells remain to be elucidated. This study aims to describe the effects of three members of TGFb protein family (TGFb, BMP-7 and GDF-15) on osteoclast differentiation of murine cell line RAW264.7. These proteins are secreted by prostate cancer cell line LNCaP, possess strong morphogenic effects and are supposed to influence bone microenvironment significantly. TGFb, BMP-7 or GDF-15 affected efficiency of osteoclast differentiation strongly. While TGFb treatment stimulated RANKL-induced differentiation, BMP-7 and GDF-15 cytokines clearly reduced differentiation potential of RAW264.7 cells to active osteoclasts. In contrast to RANKL/TGFb that induced expression of several osteoclast-associated genes, RANKL/GDF-15 and RANKL/BMP-7 suppressed it. According to these we document that different members of the TGFb protein family differently regulate signaling in osteoclasts and consequently modulate the final cellular answer.