KEGG   PATHWAY: mdo04380
Entry
mdo04380                    Pathway                                
Name
Osteoclast differentiation - Monodelphis domestica (gray short-tailed opossum)
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
mdo04380  Osteoclast differentiation
mdo04380

Other DBs
GO: 0030316
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100033077  CSF1; colony stimulating factor 1 [KO:K05453]
100028926  CSF1R; colony stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
100022894  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100010412  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100017332  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100024769  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
100019317  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100032726  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
100616957  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
100014564  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100019947  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100027373  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100031565  IFNGR1; interferon gamma receptor 1 [KO:K05132]
103106298  IFNGR2; interferon gamma receptor 2 [KO:K05133]
100028917  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
103105940  IL1A; interleukin 1 alpha [KO:K04383]
100026024  IL1B; interleukin 1 beta [KO:K04519]
100017751  IL1R1; interleukin 1 receptor type 1 [KO:K04386]
100023069  TNF; tumor necrosis factor [KO:K03156]
103104450  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
100019183  TGFB1; transforming growth factor beta 1 [KO:K13375]
100017548  TGFB2; transforming growth factor beta 2 [KO:K13376]
100011507  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:2.7.11.30]
100031897  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:2.7.11.30]
100011641  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
100024621  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
100031818  TNFRSF11B; TNF receptor superfamily member 11b [KO:K05148]
100017243  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
100010055  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
100025680  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
100022459  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
100020668  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100027952  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100618518  RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253]
100029209  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
100019975  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100012432  TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403]
100026855  TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
100022918  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100033031  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100011769  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100030053  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100014446  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100028435  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
100023153  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
100021258  IFNB1; interferon beta [KO:K05415]
100018410  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100029049  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
100010279  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100010891  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100026324  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100028821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100026752  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100028089  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100618895  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100018285  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
100010781  FOSB; FosB proto-oncogene, AP-1 transcription factor subunit [KO:K09029]
100026446  FOSL2; FOS like 2, AP-1 transcription factor subunit [KO:K09030]
100616977  FOSL1; FOS like 1, AP-1 transcription factor subunit [KO:K04502]
100018774  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103092114  JUND; JunD proto-oncogene, AP-1 transcription factor subunit [KO:K04449]
100009986  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K09028]
100026992  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
100026086  uncharacterized LOC100026086 [KO:K08009]
100024184  NCF2; neutrophil cytosolic factor 2 [KO:K08010]
100014144  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
100025111  NCF4; neutrophil cytosolic factor 4 [KO:K08012]
100022891  BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
100019245  TEC; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
100026419  osteoclast-associated immunoglobulin-like receptor [KO:K14377]
103095372  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K14377]
103105947  leukocyte immunoglobulin-like receptor subfamily B member 4 [KO:K06512]
103101413  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
100028145  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
103103214  leukocyte immunoglobulin-like receptor subfamily B member 4 [KO:K06512]
107649186  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
103092129  leukocyte immunoglobulin-like receptor subfamily B member 5 [KO:K06512]
103100828  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
103103515  leukocyte-associated immunoglobulin-like receptor 1 [KO:K06512]
103093099  FCRL6; Fc receptor like 6 [KO:K06498]
100015202  low affinity immunoglobulin gamma Fc region receptor II-like [KO:K12560]
100619042  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b [KO:K12560]
100015157  low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
100030137  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
100023014  SIRPA; signal regulatory protein alpha [KO:K06551]
100013350  uncharacterized LOC100013350 [KO:K06551]
103093683  signal-regulatory protein beta-1-like [KO:K06551]
100016660  TYROBP; TYRO protein tyrosine kinase binding protein [KO:K07992]
100028356  tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
100022658  BLNK; B-cell linker [KO:K07371]
100026299  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100027579  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
100013305  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100010212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100025596  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100014945  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
100619889  sarcoplasmic/endoplasmic reticulum calcium ATPase 3-like [KO:K05853] [EC:7.2.2.10]
100015597  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
103098393  sarcoplasmic/endoplasmic reticulum calcium ATPase 3-like [KO:K05853] [EC:7.2.2.10]
100029449  TMEM64; transmembrane protein 64 [KO:K26770]
100014900  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
100011077  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
100033104  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
100033302  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
100015956  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
100014049  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100016353  SPI1; Spi-1 proto-oncogene [KO:K09438]
100020078  MITF; melanogenesis associated transcription factor [KO:K09455]
100017449  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
100010467  ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
100026720  CALCR; calcitonin receptor [KO:K04576]
100025359  ITGB3; integrin subunit beta 3 [KO:K06493]
100025091  PPARG; peroxisome proliferator activated receptor gamma [KO:K08530]
103092556  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
100031307  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
100012931  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
100030758  IRF9; interferon regulatory factor 9 [KO:K04693]
100616780  suppressor of cytokine signaling 1-like [KO:K04694]
100026656  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100017910  GAB2; GRB2 associated binding protein 2 [KO:K08091]
100014654  FHL2; four and a half LIM domains 2 [KO:K14380]
100014031  CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
100032104  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
mdo04010  MAPK signaling pathway
mdo04020  Calcium signaling pathway
mdo04064  NF-kappa B signaling pathway
mdo04151  PI3K-Akt signaling pathway
mdo04630  JAK-STAT signaling pathway
KO pathway
ko04380   
LinkDB

DBGET integrated database retrieval system