Mouse genetics have uncovered new paradigms in bone biology.
In the past decade, mouse models have improved our understanding of bone biology. Given the fact that osteoporosis is among the most common diseases, this review will focus on the regulation of differentiation and function of the bone-resorbing osteoclasts and the bone-forming osteoblasts. Mouse genetic studies have revealed a cascade controlling osteoclastogenesis that includes the recently discovered molecules osteoprotegerin, RANK and RANK ligand. In terms of osteoblast differentiation, CBFA1 and Indian hedgehog have been identified as activators. Moreover, recent evidence demonstrates that osteoblast function is, at least in part, controlled by the hypothalamus.
Günther
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Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Schinke
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D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit; D006023:Glycoproteins / Q000502:physiology; D053823:Hedgehog Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice / Q000235:genetics*; D009363:Neoplasm Proteins; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D053244:Osteoprotegerin; D011506:Proteins / Q000502:physiology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology
D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006023:Glycoproteins; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D053244:Osteoprotegerin; D011506:Proteins; 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; D015534:Trans-Activators; D014157:Transcription Factors