KEGG   PATHWAY: prob04380
Entry
prob04380                   Pathway                                
Name
Osteoclast differentiation - Phodopus roborovskii (desert hamster)
Description
The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast.
Class
Organismal Systems; Development and regeneration
Pathway map
prob04380  Osteoclast differentiation
prob04380

Other DBs
GO: 0030316
Organism
Phodopus roborovskii (desert hamster) [GN:prob]
Gene
127216878  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
127234180  Csf1r; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
127219174  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
127228340  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
127216731  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
127226948  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
127223328  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
127238024  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127213428  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127217216  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127225197  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
127220972  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
127223664  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127231187  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127239025  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127215720  Ifng; interferon gamma [KO:K04687]
127215047  Ifngr1; interferon gamma receptor 1 [KO:K05132]
127227515  Ifngr2; interferon gamma receptor 2 [KO:K05133]
127226208  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
127221461  Il1a; interleukin-1 alpha [KO:K04383]
127221462  Il1b; interleukin-1 beta [KO:K04519]
127236676  Il1r1; interleukin-1 receptor type 1 [KO:K04386]
127224347  Tnf; tumor necrosis factor [KO:K03156]
127213032  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
127238425  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
127223750  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
127224670  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
127234956  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
127230483  Tnfsf11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
127236303  Tnfrsf11a; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
127235300  Tnfrsf11b; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
127222603  Traf2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
127222196  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
127225402  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
127215149  Fyn; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
127216792  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
127233576  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
127238844  Relb; transcription factor RelB isoform X1 [KO:K09253]
127233275  Nfkb2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
127224461  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
127225789  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
127237647  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
127217362  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
127220313  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
127230598  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
127228707  Rela; transcription factor p65 isoform X1 [KO:K04735]
127222971  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
127223216  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
127225333  nuclear factor of activated T-cells, cytoplasmic 2-like [KO:K17332]
127235061  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
127224840  Ifnb1; interferon beta [KO:K05415]
127231875  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
127218712  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
127224210  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
127224217  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
127225455  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
127225941  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
127225942  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
127237193  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
127235390  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
127219360  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
127232178  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
127230991  Fos; protein c-Fos [KO:K04379]
127239036  Fosb; protein FosB isoform X1 [KO:K09029]
127220107  Fosl2; fos-related antigen 2 [KO:K09030]
127228692  Fosl1; fos-related antigen 1 [KO:K04502]
127224952  Jun; transcription factor Jun [KO:K04448]
127217209  Jund; transcription factor JunD [KO:K04449]
127229912  Junb; transcription factor JunB [KO:K09028]
127237270  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
127217829  Nox1; NADPH oxidase 1 [KO:K08008]
127234514  cytochrome b-245 light chain [KO:K08009]
127223415  Ncf2; neutrophil cytosol factor 2 [KO:K08010]
127236897  Ncf1; neutrophil cytosol factor 1 [KO:K08011]
127225743  Ncf4; neutrophil cytosol factor 4 [KO:K08012]
127218588  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
127232110  Tec; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
127238959  Oscar; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
127238408  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
127238410  leukocyte immunoglobulin-like receptor subfamily A member 6 isoform X1 [KO:K06512]
127238413  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
127238414  leukocyte immunoglobulin-like receptor subfamily B member 4A isoform X1 [KO:K06512]
127238416  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
127238512  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
127238513  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
127238517  LOW QUALITY PROTEIN: neutrophil immunoglobulin-like receptor 1 [KO:K06512]
127238518  leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
127238697  leukocyte immunoglobulin-like receptor subfamily B member 3A [KO:K06512]
127238698  leukocyte immunoglobulin-like receptor subfamily A member 5 isoform X1 [KO:K06512]
127238950  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
127238951  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
127238963  leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
127232830  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
127223560  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor II-a [KO:K06472]
127223559  Fcgr2b; low affinity immunoglobulin gamma Fc region receptor II-b isoform X1 [KO:K12560]
127223278  low affinity immunoglobulin gamma Fc region receptor III-A [KO:K06463]
127236626  Trem2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
127233070  LOW QUALITY PROTEIN: signal-regulatory protein beta-1-like [KO:K06551]
127221271  Sirpa; tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
127238750  Tyrobp; TYRO protein tyrosine kinase-binding protein [KO:K07992]
127229235  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
127233357  Blnk; B-cell linker protein [KO:K07371]
127219433  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
127234658  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
127236214  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127213143  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127224232  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127228318  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
127216072  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
127218952  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
127231982  Tmem64; transmembrane protein 64 [KO:K26770]
127222969  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
127230207  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127214138  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127224691  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
127233971  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
127235144  Camk4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
127226375  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
127222253  Spi1; transcription factor PU.1 isoform X1 [KO:K09438]
127236072  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
127232730  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
127231328  Acp5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
127216498  Calcr; calcitonin receptor [KO:K04576]
127217777  Itgb3; integrin beta-3 [KO:K06493]
127236259  Pparg; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
127227514  Ifnar1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
127227512  Ifnar2; interferon alpha/beta receptor 2 [KO:K05131]
127224978  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
127231265  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
127215637  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
127230369  Irf9; interferon regulatory factor 9 [KO:K04693]
127223018  LOW QUALITY PROTEIN: suppressor of cytokine signaling 1-like [KO:K04694]
127219667  Socs1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
127219795  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
127227914  Gab2; GRB2-associated-binding protein 2 [KO:K08091]
127236544  Fhl2; four and a half LIM domains protein 2 [KO:K14380]
127229986  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
127219353  Sqstm1; sequestosome-1 isoform X1 [KO:K14381]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:18722561
  Authors
Caetano-Lopes J, Canhao H, Fonseca JE
  Title
Osteoimmunology--the hidden immune regulation of bone.
  Journal
Autoimmun Rev 8:250-5 (2009)
DOI:10.1016/j.autrev.2008.07.038
Reference
PMID:18451259
  Authors
Lorenzo J, Horowitz M, Choi Y
  Title
Osteoimmunology: interactions of the bone and immune system.
  Journal
Endocr Rev 29:403-40 (2008)
DOI:10.1210/er.2007-0038
Reference
PMID:17869613
  Authors
David JP
  Title
Osteoimmunology: a view from the bone.
  Journal
Adv Immunol 95:149-65 (2007)
DOI:10.1016/S0065-2776(07)95005-1
Reference
PMID:16313342
  Authors
Jimi E, Ghosh S
  Title
Role of nuclear factor-kappaB in the immune system and bone.
  Journal
Immunol Rev 208:80-7 (2005)
DOI:10.1111/j.0105-2896.2005.00329.x
Reference
PMID:12748652
  Authors
Boyle WJ, Simonet WS, Lacey DL
  Title
Osteoclast differentiation and activation.
  Journal
Nature 423:337-42 (2003)
DOI:10.1038/nature01658
Reference
PMID:17633024
  Authors
Darnay BG, Besse A, Poblenz AT, Lamothe B, Jacoby JJ
  Title
TRAFs in RANK signaling.
  Journal
Adv Exp Med Biol 597:152-9 (2007)
DOI:10.1007/978-0-387-70630-6_12
Reference
PMID:15122243
  Authors
Baron R
  Title
Arming the osteoclast.
  Journal
Nat Med 10:458-60 (2004)
DOI:10.1038/nm0504-458
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20703218
  Authors
Krum SA, Chang J, Miranda-Carboni G, Wang CY
  Title
Novel functions for NFkappaB: inhibition of bone formation.
  Journal
Nat Rev Rheumatol 6:607-11 (2010)
DOI:10.1038/nrrheum.2010.133
Reference
PMID:15817678
  Authors
Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY
  Title
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation.
  Journal
Blood 106:852-9 (2005)
DOI:10.1182/blood-2004-09-3662
Reference
PMID:18329366
  Authors
Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K, Yasuda H, Takai T, Kodama T, Morio T, Geha RS, Kitamura D, Kurosaki T, Ellmeier W, Takayanagi H
  Title
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals.
  Journal
Cell 132:794-806 (2008)
DOI:10.1016/j.cell.2007.12.037
Reference
PMID:15546140
  Authors
Takayanagi H, Kim S, Koga T, Taniguchi T
  Title
Stat1-mediated cytoplasmic attenuation in osteoimmunology.
  Journal
J Cell Biochem 94:232-40 (2005)
DOI:10.1002/jcb.20316
Reference
PMID:18382763
  Authors
Jin W, Chang M, Paul EM, Babu G, Lee AJ, Reiley W, Wright A, Zhang M, You J, Sun SC
  Title
Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice.
  Journal
J Clin Invest 118:1858-66 (2008)
DOI:10.1172/JCI34257
Reference
PMID:16184196
  Authors
Bai S, Kitaura H, Zhao H, Chen J, Muller JM, Schule R, Darnay B, Novack DV, Ross FP, Teitelbaum SL
  Title
FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner.
  Journal
J Clin Invest 115:2742-51 (2005)
DOI:10.1172/JCI24921
Reference
PMID:12110142
  Authors
Takayanagi H, Kim S, Taniguchi T
  Title
Signaling crosstalk between RANKL and interferons in osteoclast differentiation.
  Journal
Arthritis Res 4 Suppl 3:S227-32 (2002)
DOI:10.1186/ar581
Related
pathway
prob04010  MAPK signaling pathway
prob04020  Calcium signaling pathway
prob04064  NF-kappa B signaling pathway
prob04151  PI3K-Akt signaling pathway
prob04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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