KEGG   PATHWAY: aml04380
Entry
aml04380                    Pathway                                
Name
Osteoclast differentiation - Ailuropoda melanoleuca (giant panda)
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
aml04380  Osteoclast differentiation
aml04380

Other DBs
GO: 0030316
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100467411  CSF1; macrophage colony-stimulating factor 1 isoform X2 [KO:K05453]
100472252  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X2 [KO:K05090] [EC:2.7.10.1]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100462659  IFNG; interferon gamma precursor [KO:K04687]
100473768  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100481672  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100474026  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100481122  IL1A; interleukin-1 alpha [KO:K04383]
100480874  IL1B; interleukin-1 beta [KO:K04519]
100472991  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
100471563  TNF; tumor necrosis factor [KO:K03156]
100479926  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100470703  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
100463584  TGFB2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
100475698  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
100482939  TGFBR2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
100483079  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
100483336  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
100465761  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
100474087  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
100483216  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100477981  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
100470931  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100472260  MAP3K14; mitogen-activated protein kinase kinase kinase 14 isoform X1 [KO:K04466] [EC:2.7.11.25]
100464675  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100477158  RELB; LOW QUALITY PROTEIN: transcription factor RelB [KO:K09253]
100474781  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X2 [KO:K04469]
100466506  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
100484077  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform X3 [KO:K04403]
100468085  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X1 [KO:K04404]
100470223  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100471679  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100466997  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100480158  RELA; transcription factor p65 isoform X1 [KO:K04735]
100467906  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100464798  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X4 [KO:K17332]
100470861  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
100476556  IFNB1; interferon beta [KO:K05415]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100469111  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
100465223  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100465476  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100480235  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100480483  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100475975  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
100477951  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100482196  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100477600  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
100474867  FOS; proto-oncogene c-Fos [KO:K04379]
100480695  FOSB; protein fosB [KO:K09029]
100470557  FOSL2; fos-related antigen 2 isoform X1 [KO:K09030]
100484750  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
100483834  JUN; transcription factor AP-1 [KO:K04448]
100476526  JUND; transcription factor jun-D [KO:K04449]
100478228  JUNB; transcription factor jun-B [KO:K09028]
100465648  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100470141  NOX1; NADPH oxidase 1 isoform X1 [KO:K08008]
100482979  cytochrome b-245 light chain isoform X3 [KO:K08009]
100476832  NCF2; neutrophil cytosol factor 2 [KO:K08010]
100472606  NCF1; neutrophil cytosol factor 1 [KO:K08011]
100468228  NCF4; neutrophil cytosol factor 4 [KO:K08012]
100472303  BTK; tyrosine-protein kinase BTK isoform X3 [KO:K07370] [EC:2.7.10.2]
100463806  TEC; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
100466769  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
100475665  leukocyte immunoglobulin-like receptor subfamily A member 6 isoform X1 [KO:K06512]
100465121  leukocyte immunoglobulin-like receptor subfamily A member 2 isoform X1 [KO:K06512]
100468029  leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
100474098  leukocyte immunoglobulin-like receptor subfamily A member 2 [KO:K06512]
100467775  leukocyte immunoglobulin-like receptor subfamily B member 2 [KO:K06512]
100468283  leukocyte immunoglobulin-like receptor subfamily A member 6 isoform X1 [KO:K06512]
100468532  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
117797931  leukocyte immunoglobulin-like receptor subfamily A member 6 [KO:K06512]
117795059  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
100471819  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
100479420  low affinity immunoglobulin gamma Fc region receptor II isoform X2 [KO:K12560]
100481923  low affinity immunoglobulin gamma Fc region receptor III-B isoform X1 [KO:K06463]
100466531  TREM2; triggering receptor expressed on myeloid cells 2 isoform X2 [KO:K14378]
100466571  SIRPA; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
100468887  tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
100474857  signal-regulatory protein beta-1 isoform X1 [KO:K06551]
100464540  signal-regulatory protein beta-1 isoform X1 [KO:K06551]
100477572  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X2 [KO:K07992]
100474543  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
100481331  BLNK; B-cell linker protein isoform X3 [KO:K07371]
100463836  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100481994  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100465699  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X6 [KO:K05853] [EC:7.2.2.10]
100470716  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
100465047  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100481015  TMEM64; transmembrane protein 64 [KO:K26770]
100477289  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
100467653  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100474970  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100474742  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100467683  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100473015  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100477711  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100476314  SPI1; transcription factor PU.1 isoform X3 [KO:K09438]
100471143  MITF; microphthalmia-associated transcription factor isoform X3 [KO:K09455]
100483004  CTSK; cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
100476360  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
100475876  CALCR; calcitonin receptor [KO:K04576]
100476256  ITGB3; integrin beta-3 [KO:K06493]
100482938  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
100481921  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
100482679  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
100473460  JAK1; tyrosine-protein kinase JAK1 isoform X2 [KO:K11217] [EC:2.7.10.2]
100468422  TYK2; LOW QUALITY PROTEIN: non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100472167  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
100475480  IRF9; interferon regulatory factor 9 [KO:K04693]
100480183  SOCS1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
100475555  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100469823  GAB2; GRB2-associated-binding protein 2 isoform X6 [KO:K08091]
100474940  FHL2; four and a half LIM domains protein 2 [KO:K14380]
100467467  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
100469252  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
aml04010  MAPK signaling pathway
aml04020  Calcium signaling pathway
aml04064  NF-kappa B signaling pathway
aml04151  PI3K-Akt signaling pathway
aml04630  JAK-STAT signaling pathway
KO pathway
ko04380   
LinkDB

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