Sandbox:Hannan: Difference between revisions
Hannan Javed (talk | contribs) No edit summary |
Hannan Javed (talk | contribs) No edit summary |
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* produced by osteocytes and osteoblasts and is activated by osteoclasts | * produced by osteocytes and osteoblasts and is activated by osteoclasts | ||
* primary effect in bone marrow is the inhibition of terminal differentiation of osteoblasts | * primary effect in bone marrow is the inhibition of terminal differentiation of osteoblasts | ||
|Inhibition of Transforming Growth Factor-β have been shown to prevent myeloma cells to block osteoblastic differentiation | |Inhibition of Transforming Growth Factor-β have been shown to prevent myeloma cells to block osteoblastic differentiation. | ||
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|'''Bone morphogenetic proteins (BMPs)''' | |'''Bone morphogenetic proteins (BMPs)''' | ||
* belong to TGFβ superfamily | * belong to TGFβ superfamily | ||
* promote osteoblastogenesis through Smad-dependent and Smad-independent pathways | * promote osteoblastogenesis through Smad-dependent and Smad-independent pathways | ||
|Myeloma cells express negative regulators of bone morphogenetic proteins that result in decreased activity of these proteins which in turn causes decreased osteoblastogenesis | |Myeloma cells express negative regulators of bone morphogenetic proteins that result in decreased activity of these proteins which in turn causes decreased osteoblastogenesis. | ||
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|'''Hepatocyte growth factor (HGF)''' | |'''Hepatocyte growth factor (HGF)''' | ||
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|'''Interleukin 3 (IL-3)''' | |'''Interleukin 3 (IL-3)''' | ||
* inhibits BMP-induced osteoblastogenesis, thought to be mediated indirectly by increasing CD45+ hematopoietic cells | * inhibits BMP-induced osteoblastogenesis, thought to be mediated indirectly by increasing CD45+ hematopoietic cells | ||
|Elevated levels had been demonstrated in bone marrow of myeloma patients | |Elevated levels had been demonstrated in bone marrow of myeloma patients. | ||
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|'''Interleukin 7 (IL-7)''' | |'''Interleukin 7 (IL-7)''' | ||
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** decreased osteoblasts stimulation and maturation | ** decreased osteoblasts stimulation and maturation | ||
** decreased Runx2/CBFA1 activity | ** decreased Runx2/CBFA1 activity | ||
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|'''Growth factor independence-1 (GFI1)''' | |||
* a transcriptional repressor that causes decreased expression of RUNX2 | |||
|Bone marrow stromal cells (BMSCs) in myeloma patients have been shown to over-express growth factor independence-1 (GFI1). | |||
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|'''Tissue necrosis factor-α (TNF-α)''' | |||
* inhibits osteoblast differentiation through | |||
** inhibits osteoblast precursor recruitment | |||
** suppresses RUNX2 and its transcriptional co-activator, TAZ | |||
|Tissue necrosis factor-α (TNF-α) levels are increased in multiple myeloma and it is thought to play a complex role in pathogenesis of multiple myeloma. | |||
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|'''Adiponectin''' | |||
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Revision as of 20:15, 29 October 2018
Molecular pathways and factors associated with osteoblastic activity | Association with multiple myeloma |
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Wingless and integration-1 (Wnt) signaling
Activation of Wnt pathway → binding of Wnt ligands to Wnt co-receptors LRP5/6 and one trans-membrane receptor of the FDZ family → formation of DVL–Axin–FRAT1–GSK-3β complex → translocation of β-catenin from cytoplasm to nucleus → activation of T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors → ↑ bone formation and ↓ bone resorption
Formation of WNT ligand–receptor tyrosine kinase-like orphan receptor 2 (ROR2) or the receptor-like tyrosine kinase (RYK)–FZD–DVL complex → activation of one of these 3 pathways: 1) Disheveled-associated activator of morphogenesis 1 (DAAM1)–RHO–RHO-associated kinase (ROCK) pathway; 2) RAC–Jun kinase (JNK)–RUNX2 pathway; WNT–Ca2+ pathway
|
Dickkopf 1 (Dkk-1)
Sclerostin
Secreted frizzled related protein-2 (sFRP-2)
Periostin
Runt-related transcription factor 2 (Runx2)/corebinding factor runt domain alpha subunit 1 (CBFA1)
|
Transforming growth factor-β (TGF-β)
|
Inhibition of Transforming Growth Factor-β have been shown to prevent myeloma cells to block osteoblastic differentiation. |
Bone morphogenetic proteins (BMPs)
|
Myeloma cells express negative regulators of bone morphogenetic proteins that result in decreased activity of these proteins which in turn causes decreased osteoblastogenesis. |
Hepatocyte growth factor (HGF)
|
|
Interleukin 3 (IL-3)
|
Elevated levels had been demonstrated in bone marrow of myeloma patients. |
Interleukin 7 (IL-7)
|
|
Growth factor independence-1 (GFI1)
|
Bone marrow stromal cells (BMSCs) in myeloma patients have been shown to over-express growth factor independence-1 (GFI1). |
Tissue necrosis factor-α (TNF-α)
|
Tissue necrosis factor-α (TNF-α) levels are increased in multiple myeloma and it is thought to play a complex role in pathogenesis of multiple myeloma. |
Adiponectin |