Resumo

MIKAN V, JOSE FERNANDO  e  OLIVEROS A, WILLIAM DARÍO. OSTEOCLASTOGENESIS AND BONE DISEASES. rev.fac.med [online]. 2007, vol.15, n.2, pp.261-270. ISSN 0121-5256.

Osteoclasts are specialised cells that work together with osteoblast to keep bone homeostasis. The molecules macrophage colony stimulating factor (CSF-1) and receptor-associate to the nuclear kappa-beta ligand (RANKL) play a key role in the induction and development of osteoclast (osteoclastogenesis) from granulocyte-macrophage cells. Osteoclastogenesis involve at least 24 genes on the patway RANK/RANKL/OPG, which differential expression regulates resorption and bone density. Signalling from the membrane receptor RANK to the proteins that activate specific osteoclast lineage genes (e.g. TRAP, CATK, integrin β3, among others), is made through five protein-kinase cascades, all of them belonging to the cytoplasmic protein TRAF-6 pathway and being the nuclear factor NF-κΒ the most important one. Some epigenetic factors, molecules that mediate response to hormones and cytokines that are involved in the control of bone density and homeostasis have been identified as intracellular signaling peptides of the osteoclast pathway. However a detailed comprehension of the osteoclast regulation has not been achieved. The understanding of the RANK pathway and those related to it, will enable the proposal of better and more integral approximations to handle osteoporosis and other pathologies, so that it would contribute to solve musculoskeletal or metabolic degenerative diseases. The fact that mutations on the RANK and OPG genes cause severe illness on the human bone tissue suggest that the inhibition of the RANK pathway could be a therapeutic approach as treatment for diseases where excessive resorption or bone remodeling prevail, which could open new possibilities for research groups in the fields of genetic therapy and pharmacogenetics aiming for products that could impact a big population and a growing market.

Palavras-chave : osteoclast; receptor activator of nuclear factor-kappa beta (RANK); receptor activator of nuclear factor kappa beta ligand (RANKL); osteoprotegerin (OPG); macrophage colony-stimulating factor (CSF-1).