KEGG   PATHWAY: oaa04380
Entry
oaa04380                    Pathway                                
Name
Osteoclast differentiation - Ornithorhynchus anatinus (platypus)
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
oaa04380  Osteoclast differentiation
oaa04380

Other DBs
GO: 0030316
Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
100073393  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
100073424  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100073613  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100073740  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X1 [KO:K05853] [EC:7.2.2.10]
100073776  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100073788  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100073798  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100074213  BLNK; B-cell linker protein isoform X1 [KO:K07371]
100074273  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100074478  SQSTM1; sequestosome-1 isoform X2 [KO:K14381]
100074633  RELA; transcription factor p65 isoform X1 [KO:K04735]
100074866  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100075021  FOS; proto-oncogene c-Fos [KO:K04379]
100075749  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100075806  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100076033  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:2.7.11.24]
100076220  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100076229  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100076432  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
100076517  [KO:K05869] [EC:2.7.11.17]
100076541  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
100076776  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100076965  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100077058  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100077740  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
100077893  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
100078190  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
100078394  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
100078396  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
100078459  FOSL2; fos-related antigen 2 [KO:K09030]
100078507  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100078574  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100078925  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100079362  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
100079514  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
100079755  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
100080176  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
100080187  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100080362  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100080679  FHL2; four and a half LIM domains protein 2 [KO:K14380]
100080852  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
100080912  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
100081473  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100082075  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100082351  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100082421  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100082590  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100082925  IFNB1; interferon beta [KO:K05415]
100082981  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
100083320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100083438  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100083477  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
100083665  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
100083819  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100083890  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100084001  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
100084073  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
100084242  [KO:K08009]
100084998  TEC; tyrosine-protein kinase Tec isoform X3 [KO:K07364] [EC:2.7.10.2]
100085440  [KO:K07992]
100085480  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100085554  MAP3K14; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100085643  TNF; tumor necrosis factor [KO:K03156]
100085735  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
100085817  NCF2; neutrophil cytosol factor 2 [KO:K08010]
100085930  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
100086183  NCF4; neutrophil cytosol factor 4 isoform X1 [KO:K08012]
100086258  ATP2A3; LOW QUALITY PROTEIN: sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
100086270  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100086487  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100086997  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B isoform X1 [KO:K05148]
100087119  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
100087266  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
100087467  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100087549  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
100088176  FOSL1; fos-related antigen 1 [KO:K04502]
100088286  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
100088770  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100088800  TMEM64; transmembrane protein 64 [KO:K26770]
100088825  NCF1; neutrophil cytosol factor 1 [KO:K08011]
100089276  JUNB; transcription factor jun-B [KO:K09028]
100089532  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
100089737  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X3 [KO:K04431] [EC:2.7.12.2]
100090081  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100090267  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100090302  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100090868  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
100091078  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
100091330  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100091501  [KO:K06463]
100091969  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100092264  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100092358  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
100092580  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
100092694  JUND; transcription factor jun-D [KO:K04449]
100093026  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100093310  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100093395  [KO:K06498]
100681066  [KO:K03173] [EC:2.3.2.27]
100681576  TYK2; LOW QUALITY PROTEIN: non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100681935  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
103164954  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103165236  IRF9; interferon regulatory factor 9 [KO:K04693]
103165286  [KO:K04519]
103167117  [KO:K07992]
103167126  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
103167269  [KO:K05855] [EC:2.7.10.2]
103169645  [KO:K06463]
103170597  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
103170687  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
107547075  FOSB; protein fosB isoform X1 [KO:K09029]
114806184  [KO:K06551]
114808724  [KO:K04449]
114808729  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
114809105  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
114812005  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
114812073  RELB; LOW QUALITY PROTEIN: transcription factor RelB [KO:K09253]
114813796  CALCR; calcitonin receptor [KO:K04576]
114816636  [KO:K04694]
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
oaa04010  MAPK signaling pathway
oaa04020  Calcium signaling pathway
oaa04064  NF-kappa B signaling pathway
oaa04151  PI3K-Akt signaling pathway
oaa04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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