Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies

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• 作者：Pierre J. Marie (1) (2)
  
  1. INSERM UMR-1132 ; H么pital Lariboisi猫re ; 2 rue Ambroise Par茅 ; 75475 ; Paris Cedex 10 ; France
  2. Universit茅 Paris Diderot ; Sorbonne Paris Cit茅 ; Paris ; France
  
• 关键词：Bone formation ; Osteoporosis ; Skeletal dysplasias ; Genetic mutations ; Osteosarcoma ; Treatments
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：72
• 期：7
• 页码：1347-1361
• 全文大小：668 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.