Novel osteoclast signaling mechanisms
Abstract
Osteoclasts are cells of monocyte/macrophage origin that degrade bone matrix. Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast differentiation in the presence of macrophage colony-stimulating factor. RANKL activates the tumor necrosis factor receptor-associated factor 6, c-Fos, and calcium signaling pathways, all of which are indispensable for the induction and activation of nuclear factor of activated T cells (NFAT) c1. NFATc1 is the master transcription factor for osteoclast differentiation, which regulates many osteoclast-specific genes. Multiple immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adapters, Fc receptor common chi subunit (FcRgamma), and DNAX-activating protein (DAP) 12 mediate costimulatory signals for RANK, which activate calcium signaling through phospholipase Cgamma (PLCgamma). In addition to calcineurin-NFATc1, calcium signaling activates the CaMK-CREB (calcium/calmodulin activated kinase-cyclic AMP-response element binding protein) pathway, which also plays a critical role in osteoclastogenesis. This review summarizes recent advances in the study of signaling mechanisms of osteoclast differentiation.
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The calcineurin pathway is a key costimulatory pathway of NFATc1 and an important signaling component of a number of immune cell receptors.
“This activates cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and the calcineurin pathway [21,24,25,27], a key costimulatory pathway of NFATc1 [21,23] and an important signaling component of a number of immune cell receptors [28] (Figure 4 and Figure 5).”
From Osteoclasts and Microgravity (2020) · cites this paper as [27]
Cites
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Self-citationPLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2
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Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
- Authors
- Shinohara, M., & Takayanagi, H.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Takayanagi, Hiroshi
- ORCID
- Shinohara, Masahiro
- Venue
- Current Osteoporosis Reports
- Published
- 2007-06
- Volume
- 5
- Issue
- 2
- Pages
- 67-72
- ISSN
- 1544-1873 (ISSN-L)
- 1544-2241
- OpenAlex
- W1996109006
- Cited by
- 72
- References
- 8
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 5
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Osteoporosis Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoclastogenesis, RANKL, RANK, NFATc1, calcineurin signaling, calcium signaling, phospholipase C-gamma, ITAM signaling, FcRγ, DAP12, c-fos, NF-κB signaling, macrophage colony-stimulating factor, costimulation, bone resorption
- MeSH terms
- Humans, Osteoclasts, Osteoporosis, Calcium Signaling, NFATC Transcription Factors, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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