Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts
Open Access
- 21 February 2013
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 28 (4), 711-722
- https://doi.org/10.1002/jbmr.1885
Abstract
Osteoclasts are multinucleated myeloid lineage cells formed in response to macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL) by fusion of bone marrow–derived precursors that circulate in the blood and are attracted to sites of bone resorption in response to factors, such as sphingosine‐1 phosphate signaling. Major advances in understanding of the molecular mechanisms regulating osteoclast functions have been made in the past 20 years, mainly from mouse and human genetic studies. These have revealed that osteoclasts express and respond to proinflammatory and anti‐inflammatory cytokines. Some of these cytokines activate NF‐κB and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling to induce osteoclast formation and activity and also regulate communication with neighboring cells through signaling proteins, including ephrins and semaphorins. Osteoclasts also positively and negatively regulate immune responses and osteoblastic bone formation. These advances have led to development of new inhibitors of bone resorption that are in clinical use or in clinical trials; and more should follow, based on these advances. This article reviews current understanding of how bone resorption is regulated both positively and negatively in normal and pathologic states. © 2013 American Society for Bone and Mineral Research.Keywords
This publication has 137 references indexed in Scilit:
- Autophagy Proteins Regulate the Secretory Component of Osteoclastic Bone ResorptionDevelopmental Cell, 2011
- Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP)Journal of Bone and Mineral Research, 2011
- Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind studyThe Lancet, 2011
- Cellular mechanisms of bone remodelingReviews in Endocrine and Metabolic Disorders, 2010
- The amazing osteocyteJournal of Bone and Mineral Research, 2010
- The immune system and boneArchives of Biochemistry and Biophysics, 2010
- IKKβ activation is sufficient for RANK-independent osteoclast differentiation and osteolysisJournal of Bone and Mineral Research, 2010
- Human Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia due to TNFRSF11A (RANK) MutationsAmerican Journal of Human Genetics, 2008
- Synaptotagmin VII Regulates Bone Remodeling by Modulating Osteoclast and Osteoblast SecretionDevelopmental Cell, 2008
- Functions of RANKL/RANK/OPG in bone modeling and remodelingArchives of Biochemistry and Biophysics, 2008