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

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...

Full description

Saved in:
Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2015-04, Vol.72 (7), p.1347-1361
Main Author: Marie, Pierre J.
Format: Article
Language:English
Subjects:
Apoptosis
Biochemistry
Biodegradation
Biomedical and Life Sciences
Biomedicine
Bone diseases
Bone Diseases, Developmental - genetics
Bone Diseases, Developmental - metabolism
Bone Diseases, Developmental - physiopathology
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Bone Neoplasms - physiopathology
Cell Biology
Cell Differentiation
Cellular biology
Humans
Life Sciences
Models, Biological
Molecular biology
Osteoblasts - metabolism
Osteoblasts - physiology
Osteoporosis
Osteoporosis - genetics
Osteoporosis - metabolism
Osteoporosis - physiopathology
Review
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-014-1801-2