KEGG   PATHWAY: ssc04380
Entry
ssc04380                    Pathway                                
Name
Osteoclast differentiation - Sus scrofa (pig)
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
ssc04380  Osteoclast differentiation
ssc04380

Other DBs
GO: 0030316
Organism
Sus scrofa (pig) [GN:ssc]
Gene
100037976  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
100038019  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
100049688  TNFRSF11B; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 11B [KO:K05148]
100101471  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100125540  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
100126861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100126864  IFNGR2; interferon gamma receptor 2 precursor [KO:K05133]
100127355  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100127478  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100134857  NCF1; neutrophil cytosol factor 1 [KO:K08011]
100134969  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
100135662  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
100135663  MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
100135665  RELA; transcription factor p65 [KO:K04735]
100142665  NCF2; neutrophil cytosol factor 2 [KO:K08010]
100144486  FOS; proto-oncogene c-Fos [KO:K04379]
100144538  PIGE-108A11.3; leukocyte immunoglobulin-like receptor-like [KO:K06512]
100152055  NCF4; neutrophil cytosol factor 4 isoform X3 [KO:K08012]
100152238  IFNGR1; interferon gamma receptor 1 precursor [KO:K05132]
100152350  BLNK; B-cell linker protein [KO:K07371]
100153785  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100153829  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100155015  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100155841  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100156182  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100156630  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100158082  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100192436  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100233188  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
100233191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100307052  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
100511639  [KO:K06512]
100511843  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
100511937  [KO:K02649]
100513084  CSF1; macrophage colony-stimulating factor 1 precursor [KO:K05453]
100513532  FHL2; four and a half LIM domains protein 2 [KO:K14380]
100513609  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
100513811  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100513840  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100515364  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X3 [KO:K05869] [EC:2.7.11.17]
100516962  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
100517086  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
100517279  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100517285  [KO:K06512]
100517583  TMEM64; transmembrane protein 64 [KO:K26770]
100518131  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100518663  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
100518718  SQSTM1; sequestosome-1 isoform X1 [KO:K14381]
100518788  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
100520402  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100520418  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X5 [KO:K04431] [EC:2.7.12.2]
100521529  [KO:K06512]
100521696  [KO:K06512]
100521706  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X2 [KO:K05147]
100521736  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
100522225  [KO:K06512]
100522579  [KO:K06512]
100523358  JUNB; transcription factor jun-B [KO:K09028]
100525205  FOSL1; fos-related antigen 1 [KO:K04502]
100525227  [KO:K06512]
100533555  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
100621789  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100622460  [KO:K06512]
100622559  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100622609  RELB; transcription factor RelB isoform X1 [KO:K09253]
100622710  [KO:K06512]
100623707  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100623777  FOSL2; fos-related antigen 2 [KO:K09030]
100624191  [KO:K06512]
100624570  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
100625117  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100625946  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
100626120  [KO:K06551]
100626904  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
100627149  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100627308  BTK; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
100627903  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100736562  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100736623  [KO:K06551]
100737974  TREM2; triggering receptor expressed on myeloid cells 2 precursor [KO:K14378]
100739510  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100739707  [KO:K06551]
100739822  NOX1; NADPH oxidase 1 isoform X1 [KO:K08008]
102161654  [KO:K06551]
106508173  [KO:K06512]
110259314  JUND; LOW QUALITY PROTEIN: transcription factor jun-D [KO:K04449]
110260307  [KO:K06472]
110260605  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110261009  FOSB; LOW QUALITY PROTEIN: protein fosB [KO:K09029]
396565  IL1B2; interleukin 1, beta [KO:K04519]
396603  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X3 [KO:K04348] [EC:3.1.3.16]
396609  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
396610  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
396629  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
396655  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
396658  IFNAR1; interferon alpha/beta receptor 1 precursor [KO:K05130]
396665  TGFBR1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
396820  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
396875  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
396913  JUN; transcription factor AP-1 [KO:K04448]
396923  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
396991  IFNG; interferon gamma precursor [KO:K04687]
397020  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
397063  ITGB3; integrin beta-3 precursor [KO:K06493]
397078  TGFB1; transforming growth factor beta-1 precursor [KO:K13375]
397084  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
397086  TNF; tumor necrosis factor [KO:K03156]
397094  IL1A; interleukin-1 alpha precursor [KO:K04383]
397122  IL1B; interleukin-1 beta precursor [KO:K04519]
397202  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
397241  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
397318  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
397363  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
397405  TYROBP; TYRO protein tyrosine kinase-binding protein precursor [KO:K07992]
397414  ACP5; tartrate-resistant acid phosphatase type 5 precursor [KO:K14379] [EC:3.1.3.2]
397454  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
397507  CYBA; cytochrome b-245 light chain [KO:K08009]
397569  CTSK; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
397638  CALCR; calcitonin receptor precursor [KO:K04576]
397671  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
397684  FCGR3B; low affinity immunoglobulin gamma Fc region receptor III precursor [KO:K06463]
404277  TEC; tyrosine-protein kinase Tec isoform X2 [KO:K07364] [EC:2.7.10.2]
406188  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
414902  MITF; microphthalmia-associated transcription factor [KO:K09455]
414912  SPI1; transcription factor PU.1 [KO:K09438]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
445459  IFNB1; interferon beta precursor [KO:K05415]
493186  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
494566  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 precursor [KO:K06551]
574062  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
613130  FCGR1A; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
613131  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b precursor [KO:K12560]
751869  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
780415  IRF9; interferon regulatory factor 9 [KO:K04693]
791125  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
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
ssc04010  MAPK signaling pathway
ssc04020  Calcium signaling pathway
ssc04064  NF-kappa B signaling pathway
ssc04151  PI3K-Akt signaling pathway
ssc04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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