KEGG   PATHWAY: tup04380
Entry
tup04380                    Pathway                                
Name
Osteoclast differentiation - Tupaia chinensis (Chinese tree shrew)
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
tup04380  Osteoclast differentiation
tup04380

Other DBs
GO: 0030316
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102492960  CSF1; colony stimulating factor 1 [KO:K05453]
102491581  CSF1R; colony stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106736453  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102470542  IFNG; interferon gamma [KO:K04687]
102475588  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102481577  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102476590  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102475560  IL1A; interleukin 1 alpha [KO:K04383]
102475138  IL1B; interleukin 1 beta [KO:K04519]
102492414  IL1R1; interleukin 1 receptor type 1 [KO:K04386]
102497973  TNF; tumor necrosis factor [KO:K03156]
102493692  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102488524  TGFB1; transforming growth factor beta 1 [KO:K13375]
102500482  TGFB2; transforming growth factor beta 2 [KO:K13376]
102476700  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
102486518  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
102487682  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
102482158  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
102495629  TNFRSF11B; TNF receptor superfamily member 11b [KO:K05148]
102473925  C8G; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102482652  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102468526  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
102498676  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102500729  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102490100  RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253]
102497537  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
102477331  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
102479566  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
102478674  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102478659  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102481120  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102493858  IFNB1; interferon beta 1 [KO:K05415]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102482054  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102487603  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102501733  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102495693  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102481241  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102500732  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102475730  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102472233  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102497095  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102483965  FOSB; FosB proto-oncogene, AP-1 transcription factor subunit [KO:K09029]
102497773  FOSL2; FOS like 2, AP-1 transcription factor subunit [KO:K09030]
102498337  FOSL1; FOS like 1, AP-1 transcription factor subunit [KO:K04502]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102468817  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K09028]
102479102  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102470131  NOX1; NADPH oxidase 1 [KO:K08008]
102471991  cytochrome b-245 light chain [KO:K08009]
102477644  NCF2; neutrophil cytosolic factor 2 [KO:K08010]
102502283  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
102499930  NCF4; neutrophil cytosolic factor 4 [KO:K08012]
102472301  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
102473462  TEC; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
102498851  OSCAR; osteoclast associated, immunoglobulin-like receptor [KO:K14377]
102500528  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
102492164  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
102500089  FCGR2B; Fc fragment of IgG receptor IIb [KO:K12560]
102499391  FCGR3B; Fc fragment of IgG receptor IIIb [KO:K06463]
102471959  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
102492791  signal-regulatory protein beta-1 isoform 3 [KO:K06551]
102482785  SIRPA; signal regulatory protein alpha [KO:K06551]
102493623  signal-regulatory protein beta-1 isoform 3-like [KO:K06551]
102502974  signal-regulatory protein beta-1 isoform 3-like [KO:K06551]
102496599  TYROBP; TYRO protein tyrosine kinase binding protein [KO:K07992]
102472653  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
102478358  BLNK; B-cell linker [KO:K07371]
102500142  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
102483786  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102473622  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102482868  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102475587  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102499870  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
102478604  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
102497660  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
106734944  sarcoplasmic/endoplasmic reticulum calcium ATPase 2-like [KO:K05853] [EC:7.2.2.10]
102499974  TMEM64; transmembrane protein 64 [KO:K26770]
102480885  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102478870  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102478627  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102478386  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102474096  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102479520  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102500092  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102475013  SPI1; Spi-1 proto-oncogene [KO:K09438]
102496638  MITF; melanogenesis associated transcription factor [KO:K09455]
102469152  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
102480931  ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
102480381  CALCR; calcitonin receptor [KO:K04576]
102486101  ITGB3; integrin subunit beta 3 [KO:K06493]
102495121  PPARG; peroxisome proliferator activated receptor gamma [KO:K08530]
102480854  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
102477904  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
102471806  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102493753  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102477989  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102495534  IRF9; interferon regulatory factor 9 [KO:K04693]
102495553  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
102486692  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102490988  GAB2; GRB2 associated binding protein 2 [KO:K08091]
102496377  FHL2; four and a half LIM domains 2 [KO:K14380]
102491060  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
102498598  SQSTM1; sequestosome 1 [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
tup04010  MAPK signaling pathway
tup04020  Calcium signaling pathway
tup04064  NF-kappa B signaling pathway
tup04151  PI3K-Akt signaling pathway
tup04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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