RANKL/RANK as key factors for osteoclast development and bone loss in arthropathies.
Osteoporosis or rheumatoid arthritis are bone diseases affecting hundreds of millions of people worldwide and thus pose a tremendous burden to health care. Ground-breaking discoveries made in basic science over the last decade shed light on the molecular mechanisms of bone metabolism and bone turnover. Thereby, it became possible over the past years to devise new and promising strategies for treating such diseases. In particular, three molecules, the receptor activator of NF-kappaB (RANK), its ligand RANKL and the decoy receptor of RANKL, osteoprotegerin (OPG), have been a major focus of scientists and pharmaceutical companies alike, since experiments using mice in which these genes have been inactivated unanimously established their pivotal role as central regulators ofosteoclast function. RANK(L) signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also fine-tunes bone homeostasis both in normal physiology and disease. Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment ofvarious bone diseases, such as cancer metastases, osteoporosis, or arthropathies.
Leibbrandt
Andreas
A
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Penninger
Josef M
JM
D000818:Animals; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology; D019703:Calcineurin / Q000378:metabolism; D006801:Humans; D007592:Joint Diseases / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin