Page last updated: 2024-10-24

positive regulation of osteoclast development

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of osteoclast development. [GOC:obol]

Positive regulation of osteoclast development is a complex and tightly controlled process that involves a cascade of signaling events, transcriptional regulation, and cell-cell interactions. Osteoclasts, the bone-resorbing cells, are derived from hematopoietic stem cells and their development is primarily driven by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL).

M-CSF binds to its receptor, c-Fms, on the surface of precursor cells, promoting their survival and proliferation. This initial step is crucial for the formation of a pool of osteoclast progenitors.

RANKL, expressed by osteoblasts and other stromal cells, binds to its receptor, RANK, on osteoclast progenitors. RANKL engagement initiates a signaling cascade that involves several intracellular adaptor proteins, including TRAF6 and c-Fos, and ultimately leads to the activation of transcription factors NFATc1 and NFκB.

NFATc1 is a master regulator of osteoclastogenesis, inducing the expression of genes essential for osteoclast function, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and calcitonin receptor. These genes are responsible for bone resorption, the process by which osteoclasts degrade bone matrix.

NFκB, another key transcription factor, plays a role in regulating the survival and differentiation of osteoclasts. It also contributes to the expression of inflammatory cytokines that can influence osteoclastogenesis.

In addition to M-CSF and RANKL, other factors can positively regulate osteoclast development. These include:

* **Interleukin-1 (IL-1):** This cytokine promotes osteoclastogenesis by enhancing RANKL expression and stimulating osteoclast precursor differentiation.
* **Tumor necrosis factor-α (TNF-α):** Similar to IL-1, TNF-α upregulates RANKL expression and promotes osteoclast formation.
* **Prostaglandins:** These lipid mediators, particularly prostaglandin E2 (PGE2), stimulate osteoclast differentiation and bone resorption.
* **Growth factors:** Several growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), can influence osteoclast development.

The precise interplay between these factors and signaling pathways is still being elucidated. However, it is clear that the positive regulation of osteoclast development is a highly coordinated process involving multiple cellular interactions and signaling cascades. This complexity underscores the importance of tightly controlling osteoclast activity to maintain bone homeostasis.'
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Proteins (3)

ProteinDefinitionTaxonomy
Sodium/hydrogen exchanger 9B2A sodium/hydrogen exchanger 9B2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q86UD5]Homo sapiens (human)
Ovarian cancer G-protein coupled receptor 1A sphingosylphosphorylcholine receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q15743]Homo sapiens (human)
Tumor necrosis factor ligand superfamily member 11A tumor necrosis factor ligand superfamily member 11 that is encoded in the genome of human. [PRO:WCB, UniProtKB:O14788]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
phloretindihydrochalconesantineoplastic agent;
plant metabolite
spd-304SPD-304: structure in first source
ogerinogerin: a GPR68 modulator; structure in first source