Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics.
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.
Zaidi
Mone
M
Department of Medicine, Geriatrics and Physiology and The Mount Sinai Bone Program, Bronx VA Geriatrics Research Education and Clinical Center, New York, New York, USA. Mone.zaidi@mssm.edu
Blair
Harry C
HC
Moonga
Baltit S
BS
Abe
Etsuko
E
Huang
Christopher L H
CL
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001862:Bone Resorption / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D002116:Calcitonin / Q000502:physiology; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000502:physiology; D002454:Cell Differentiation; D004164:Diphosphonates / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor
D000963:Antimetabolites; D002352:Carrier Proteins; D004164:Diphosphonates; D004967:Estrogens; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D002116:Calcitonin