Bone Remodeling Pathway

Preferred Label : Bone Remodeling Pathway;

NCIt synonyms : Bone Remodelling Pathway;

NCIt related terms : Bone Remodelling;

Alternative definition : BIOCARTA: Bone density and structure is maintained through a balance of bone resorption by osteoclasts and bone deposition by osteoblasts. The combination of simultaneous resorption and deposition creates continual remodeling of bone while excess osteoclast activity leads to an imbalance and a loss of bone density, causing osteoporosis. RANK (receptor activator of NF-kB ligand) is a receptor in the TNF receptor gene family that is involved in osteoclast differentiation. RANK-ligand, also called osteoprotegerin-ligand, binds to RANK, induces receptor dimerization, and activates downstream signaling. Osteoprotegerin is a decoy receptor for RANK-ligand that suppresses osteoclast activity and bone remodeling, helping to maintain balanced bone remodeling. RANK-ligand and osteoprotegerin are produced by osteoblasts and some factors regulate osteoclast activity indirectly through their action on the expression of these factors by osteoblasts. Binding of RANK-ligand to RANK activates signaling through TRAF-6. TRAF-6 induces several downstream signaling events, including activation of NF-kB, c-Fos and the kinase JNK1. Jnk-1 activation contributes to fos activation by RANK-ligand and may be involved in the modulation of RANK-ligand by other factors such as estrogen. Mice lacking the c-Fos gene have overly dense bone and decreased bone resorption due to reduced osteoclast differentiation, indicating that c-Fos is an important mediator of osteoclast differentiation. One of the results of c-Fos induction is transcriptional activation of interferon-beta. Interferon-beta binds to its receptor on neighboring osteoclast precursor cells to block RANK-ligand signaling and down-regulate c-Fos expression, inhibiting further osteoclast differentiation. Mice lacking interferon-beta or the interferon-beta receptor lose bone due to uncontrolled osteoclast activity, demonstrating the importance of this mechanism in vivo. Interferon-beta signaling could be used as a mechanism to prevent osteoporosis and other conditions involving excessive osteoclast resorption of bone. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_ranklPathway;

Details

Origin ID

C39212;

UMLS CUI

C1521997;

Automatic exact mappings (from CISMeF team)
- Bone remodeling (finding) [SNOMED CT concept]
- bone remodeling [GO term]
- bone remodeling [MeSH concept]
- bone remodeling [MeSH Descriptor]
Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Arginine-Vasopressin [NCIt concept]
- Fos-Related Antigen 1 [NCIt concept]
- Fos-Related Antigen 2 [NCIt concept]
- Interferon Alpha/Beta Receptor 1 [NCIt concept]
- Interferon Alpha/Beta Receptor 2 [NCIt concept]
- Interferon-Induced, Double-Stranded RNA-Activated Protein Kinase [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Proto-Oncogene c-Fos [NCIt concept]
- TNF Receptor-Associated Factor 6 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor Ligand Superfamily Member 11 [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 11A [NCIt concept]
pathway_has_gene_element
- AVP wt Allele [NCIt concept]
- EIF2AK2 wt Allele [NCIt concept]
- FOS wt Allele [NCIt concept]
- FOSL1 wt Allele [NCIt concept]
- FOSL2 wt Allele [NCIt concept]
- IFNAR1 wt Allele [NCIt concept]
- IFNAR2 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- TNFRSF11A wt Allele [NCIt concept]
- TNFSF11 wt Allele [NCIt concept]
- TRAF6 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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