Subject(s)
Arthritis, Rheumatoid/drug therapy , Bone Neoplasms/drug therapy , Endostatins/therapeutic use , Evidence-Based Medicine , Neovascularization, Pathologic/drug therapy , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Antirheumatic Agents/therapeutic use , HumansSubject(s)
Fractures, Bone/pathology , Osteoblasts/pathology , Stem Cells/pathology , Adult , Humans , MaleABSTRACT
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.
ABSTRACT
The protein Src homology 3 domain-binding protein 2 (SH3BP2) is a regulator of tumor necrosis factor (TNF)-alpha generation in macrophages and of osteoclast differentiation. SH3BP2 regulates bone marrow monocyte responses to macrophage and osteoclast differentiation signals downstream of the receptors for macrophage colony-stimulating factor and receptor activator of nuclear factor kappaB ligand. SH3BP2 is a potential target for the development of novel anti-TNF-alpha therapeutic interventions as well as a target for suppression of osteoclastogenesis.
