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RANK/RANKL: Regulators of Immune Responses and Bone Physiology
Author(s) -
Leibbrandt Andreas,
Penninger Josef M.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1443.016
Subject(s) - rankl , osteoclast , bone remodeling , osteoprotegerin , osteoporosis , rank ligand , medicine , cancer research , signal transduction , immune system , immunology , receptor , bioinformatics , microbiology and biotechnology , biology , activator (genetics)
Bone‐related diseases, such as osteoporosis and rheumatoid arthritis, affect hundreds of millions of people worldwide and pose a tremendous burden to health care. By deepening our understanding of the molecular mechanisms of bone metabolism and bone turnover, it became possible over the past years to devise new and promising strategies for treating such diseases. In particular, three tumor necrosis factor (TNF) family molecules, the receptor activator of NF‐κB (RANK), its ligand RANKL, and the decoy receptor of RANKL, osteoprotegerin (OPG), have attracted the attention of scientists and pharmaceutical companies alike. Genetic experiments revolving around these molecules established their pivotal role as central regulators of osteoclast development and osteoclast function. RANK‐RANKL 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. In addition, RANKL and RANK have essential roles in lymph node formation, establishment of the thymic microenvironment, and development of a lactating mammary gland during pregnancy. Consequently, novel drugs specifically targeting RANK, RANKL, and their signaling pathways in osteoclasts are expected to revolutionize the treatment of various ailments associated with bone loss, such as arthritis, periodontal disease, cancer metastases, and osteoporosis.