Publication details

Distinct effects of members of the TGFbeta proteins on differentiation of osteoclasts



Year of publication 2008
Type Article in Proceedings
Conference ELSO Proceedings - Frontiers of cellular, developmental and molecular biology
MU Faculty or unit

Faculty of Science

Field Genetics and molecular biology
Keywords TGF proteins; osteoclasts; prostate cancer
Description Cancer cells can strongly influence their microenvironment, increasing the chance to survive or form metastases. In prostate cancer the tumor cells preferentially disseminate to skeletal tissue. Mechanisms responsible for selective homing and activity of cancer cells in the bone microenvironment have not been clarified yet. Therefore, the aim of this study is to describe the effects of three members of the TGFb protein family, the TGFb1, BMP-7 and GDF-15 on osteoclast differentiation of murine macrophage cell line RAW264.7. The TGFb, BMP-7 and GDF-15 proteins are secreted by prostate cancer LNCaP cells. These proteins possess strong morphogenic effects during embryogenesis and organ formation, but they participate in the bone remodeling processes and in control of the bone microenvironment as well. We observed that TGFb1 stimulated the RANKL/MCSF-induced differentiation of RAW264.7 cells to mature osteoclasts and induced expression of several osteoclast-associated genes, such as cathepsin K, NFATc1, MITF and c-fos. In contrast, the BMP-7 and GDF-15 cytokines suppressed the RANKL/MCSF-induced osteoclast differentiation and inhibited expression of the osteoclast-associated genes. Interestingly, expression of the gene coding for carbonic anhydrase II, a gene strongly expressed during physiological osteoclast differentiation, was suppressed by TGFb1, BMP-7 and GDF-15 in RANKL/CMSF-treated RAW264.7 cells. Thus, we conclude that distinct members of the TGFb family of preoteins, produced by prostate cancer cells play specific roles in regulation of signals controlling formation of osteoclasts. This work was supported by grants 301/06/0036, 204/08/H054 of the Czech Science Foundation, MSM0021622415 of Ministry of Education, Youth and Sports of the Czech Republic (JS) and grants 204/07/0834, 310/07/0961 of the Czech Science Foundation and AV0Z50040507 and AV0Z50040702 of the Grant Agency of Academy of Sciences of the Czech Republic (KS).
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