Osteopetrosis and osteoporosis: two sides of the same coin.
Together, osteoporosis and osteopetrosis comprise a substantial proportion of the bone diseases that severely affect humans. In order to understand and effectively treat these disorders, an understanding of the mechanisms controlling bone remodelling is essential. While numerous animal models of bone disease have been generated, the lack of correlation between these animal models and human disease has limited their utility in terms of defining therapeutic strategies. The generation and analysis of cathepsin K knockout mice has resulted in a model for pycnodysostosis, a rare human osteopetrotic disease, and is now providing considerable insights into both osteoclast function and potential therapeutic strategies for the treatment of bone disease. This review highlights the importance of genes such as cathepsin K in understanding bone remodelling and illustrates a new trend towards understanding bone disease as a complete entity rather than as a series of unrelated disorders.
Lazner
F
F
Centre for Functional Genomics and Human Disease, Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
Gowen
M
M
Pavasovic
D
D
Kola
I
I
D000818:Animals; D016723:Bone Remodeling / Q000235:genetics; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D010022:Osteopetrosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D010024:Osteoporosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D053244:Osteoprotegerin; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; C494070:Ets2 protein, mouse; D006023:Glycoproteins; D053244:Osteoprotegerin; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D012097:Repressor Proteins; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse