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Osteoclastogenesis, Bone Resorption, and Osteoclast‐Based Therapeutics
Author(s) -
Zaidi Mone,
Blair Harry C,
Moonga Baltit S,
Abe Etsuko,
Huang Christopher LH
Publication year - 2003
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2003.18.4.599
Subject(s) - osteoclast , cathepsin k , bone resorption , cathepsin , microbiology and biotechnology , matrix metalloproteinase , osteoblast , rankl , secretion , biology , chemistry , endocrinology , biochemistry , enzyme , receptor , in vitro , activator (genetics)
Over the past decade, advances in molecular tools, stem cell differentiation, osteoclast and osteoblast signaling mechanisms, and genetically manipulated mice models have resulted in major breakthroughs in understanding osteoclast biology. This review focuses on key advances in our understanding of molecular mechanisms underlying the formation, function, and survival of osteoclasts. These include key signals mediating osteoclast differentiation, including PU.1, RANK, CSF‐1/ c‐fms , and src , and key specializations of the osteoclast including HCl secretion driven by H + ‐ATPase and the secretion of collagenolytic enzymes including cathepsin K and matrix metalloproteinases (MMPs). These pathways and highly expressed proteins provide targets for specific therapies to modify bone degradation. The main outstanding issues, basic and translational, will be considered in relation to the osteoclast as a target for antiresorptive therapies.