KEGG   PATHWAY: umr04380
Entry
umr04380                    Pathway                                
Name
Osteoclast differentiation - Ursus maritimus (polar bear)
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
umr04380  Osteoclast differentiation
umr04380

Other DBs
GO: 0030316
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656206  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
103656234  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
103656858  IFNG; interferon gamma [KO:K04687]
103657054  FOSB; protein fosB [KO:K09029]
103657178  RELB; transcription factor RelB [KO:K09253]
103657815  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X3 [KO:K05853] [EC:7.2.2.10]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103658194  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103658249  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b [KO:K12560]
103658250  [KO:K06463]
103658473  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
103658730  CALCR; calcitonin receptor [KO:K04576]
103658916  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103659023  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
103659308  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103659802  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103659933  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
103660092  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661275  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
103661473  TMEM64; transmembrane protein 64 isoform X1 [KO:K26770]
103661589  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
103662093  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103662150  IFNB1; interferon beta [KO:K05415]
103663059  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103663192  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
103663370  IFNGR1; interferon gamma receptor 1 [KO:K05132]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103664102  TREM2; triggering receptor expressed on myeloid cells 2 isoform X2 [KO:K14378]
103664603  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
103664784  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103665275  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103665553  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103665687  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103665883  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
103665892  ITGB3; integrin beta-3 [KO:K06493]
103665967  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103666444  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103666926  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
103667123  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
103667534  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
103667577  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
103667825  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103667893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103669544  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
103669597  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103669832  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103670095  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103670166  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
103670627  FHL2; four and a half LIM domains protein 2 [KO:K14380]
103670641  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103670861  JUN; transcription factor AP-1 [KO:K04448]
103671011  FOS; proto-oncogene c-Fos [KO:K04379]
103671340  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
103671495  IL1B; interleukin-1 beta isoform X2 [KO:K04519]
103671624  FOSL2; fos-related antigen 2 [KO:K09030]
103671864  IL1A; interleukin-1 alpha [KO:K04383]
103672241  BLNK; LOW QUALITY PROTEIN: B-cell linker protein [KO:K07371]
103672387  [KO:K09438]
103672508  NCF2; neutrophil cytosol factor 2 [KO:K08010]
103672715  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
103672871  [KO:K06512]
103672883  OSCAR; osteoclast-associated immunoglobulin-like receptor isoform X1 [KO:K14377]
103672907  [KO:K06512]
103672908  [KO:K06512]
103672987  BTK; tyrosine-protein kinase BTK isoform X2 [KO:K07370] [EC:2.7.10.2]
103672992  NOX1; NADPH oxidase 1 isoform X1 [KO:K08008]
103673110  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
103673220  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
103673221  IFNGR2; interferon gamma receptor 2 [KO:K05133]
103673318  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103673798  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
103673846  [KO:K08009]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103674247  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
103674374  [KO:K06551]
103674375  [KO:K06551]
103674501  [KO:K06551]
103674504  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1 [KO:K06551]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103675205  CSF1; macrophage colony-stimulating factor 1 [KO:K05453]
103675245  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
103675811  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103676207  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
103676418  NCF4; neutrophil cytosol factor 4 [KO:K08012]
103676518  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103676947  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103676988  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103677394  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
103677566  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
103677943  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103678081  GAB2; GRB2-associated-binding protein 2 isoform X3 [KO:K08091]
103678534  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103678627  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
103678669  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
103678725  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103679279  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
103679475  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
103679584  RELA; transcription factor p65 [KO:K04735]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103679990  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103680014  SQSTM1; sequestosome-1 [KO:K14381]
103680273  [KO:K06512]
103680276  [KO:K06512]
103680282  [KO:K06512]
103680283  [KO:K06512]
103680284  [KO:K06512]
103680286  [KO:K06512]
103681888  MAP2K7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103682015  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
103682201  JUNB; transcription factor jun-B [KO:K09028]
103682322  TNF; tumor necrosis factor [KO:K03156]
103682527  [KO:K07992]
121102517  JUND; transcription factor jun-D [KO:K04449]
121103675  SOCS1; suppressor of cytokine signaling 1 [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
umr04010  MAPK signaling pathway
umr04020  Calcium signaling pathway
umr04064  NF-kappa B signaling pathway
umr04151  PI3K-Akt signaling pathway
umr04630  JAK-STAT signaling pathway
KO pathway
ko04380   

DBGET integrated database retrieval system