Is There a Role for NFAT Inhibitors in the Prevention of Bone Destruction?
Pathologic conditions resulting from excessive bone destruction include osteoporosis, rheumatoid arthritis, metastases, periprosthetic osteolysis, cherubism, and others. A scarcity of molecular targets in bone has thwarted the development of drugs to combat these conditions. Nuclear factor of activated T-cells (NFAT) is a master regulator of osteoclastogenesis and is induced by RANKL. The immunosuppressive drugs, Cyclosporin A and Tacrolimus, inhibit osteoclast formation by targeting the NFAT/calcineurin pathway. These NFAT inhibitors should be considered in the treatment of osteoclastic hyper-resorptive syndromes.
Keywordsosteoclast NFAT Cyclosporin A Tacrolimus calcineurin
- 12.Kino T, Hatanaka H, Hashimoto M et al (1987) FK-506, a novel immunosuppressant isolated from a streptomyces. 1. Fermentation, isolation, and physico-chemical and biological characteristics. J. Antibiot. (Tokyo) 40(9):1249–1255Google Scholar