KEGG   PATHWAY: hsa04380Help
Entry
hsa04380                    Pathway                                

Name
Osteoclast differentiation - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Osteoclast differentiation
hsa04380

All organismsOrtholog table
Disease
H00436  
Osteopetrosis
H00437  
Paget's disease of bone and related disorders
H00438  
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)
H00540  
Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  
Incontinentia pigmenti
H00800  
Loeys-Dietz syndrome (LDS)
H00882  
Cocoon syndrome
H01132  
Aplastic anemia (AA)
H01187  
Tietz syndrome
H01240  
Immune thrombocytopenia (ITP)
Drug
D00742  
Etanercept (genetical recombination) (JAN)
D00746  
Interferon beta-1b (genetical recombination) (JAN)
D02598  
Infliximab (genetical recombination) (JAN)
D02934  
Anakinra (USAN/INN)
D03304  
Interferon beta (JAN)
D03684  
Denosumab (genetical recombination) (JAN)
D03736  
Doramapimod (USAN/INN)
D04554  
Interferon beta-1a (genetical recombination) (JAN)
D06634  
Relacatib (USAN/INN)
D08955  
Odanacatib (JAN/USAN)
D08963  
Pamapimod (INN/USAN)
D09386  
Talmapimod (USAN/INN)
D09602  
Dilmapimod (USAN/INN)
D09603  
Dilmapimod tosylate (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
1435  
CSF1; colony stimulating factor 1 [KO:K05453]
1436  
CSF1R; colony stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
2885  
GRB2; growth factor receptor bound protein 2 [KO:K04364]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
3458  
IFNG; interferon, gamma [KO:K04687]
3459  
IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  
IFNGR2; interferon gamma receptor 2 (interferon gamma transducer 1) [KO:K05133]
6772  
STAT1; signal transducer and activator of transcription 1 [KO:K11220]
3552  
IL1A; interleukin 1 alpha [KO:K04383]
3553  
IL1B; interleukin 1 beta [KO:K04519]
3554  
IL1R1; interleukin 1 receptor type 1 [KO:K04386]
7124  
TNF; tumor necrosis factor [KO:K03156]
7132  
TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
7040  
TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor beta 2 [KO:K13376]
7046  
TGFBR1; transforming growth factor beta receptor I [KO:K04674] [EC:2.7.11.30]
7048  
TGFBR2; transforming growth factor beta receptor II [KO:K04388] [EC:2.7.11.30]
8600  
TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
8792  
TNFRSF11A; tumor necrosis factor receptor superfamily member 11a [KO:K05147]
4982  
TNFRSF11B; tumor necrosis factor receptor superfamily member 11b [KO:K05148]
7186  
TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
7189  
TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
3932  
LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
2534  
FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
9020  
MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
5971  
RELB; v-rel avian reticuloendotheliosis viral oncogene homolog B [KO:K09253]
4791  
NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 [KO:K04469]
6885  
MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
10454  
TAB1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
23118  
TAB2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
4773  
NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
4772  
NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
3456  
IFNB1; interferon beta 1 [KO:K05415]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5608  
MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5609  
MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
2354  
FOSB; FBJ murine osteosarcoma viral oncogene homolog B [KO:K09029]
2355  
FOSL2; FOS like antigen 2 [KO:K09030]
8061  
FOSL1; FOS like antigen 1 [KO:K04502]
3725  
JUN; jun proto-oncogene [KO:K04448]
3727  
JUND; jun D proto-oncogene [KO:K04449]
3726  
JUNB; jun B proto-oncogene [KO:K09028]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
50508  
NOX3; NADPH oxidase 3 [KO:K08008]
27035  
NOX1; NADPH oxidase 1 [KO:K08008]
1536  
CYBB; cytochrome b-245, beta polypeptide [KO:K08008]
1535  
CYBA; cytochrome b-245 alpha chain [KO:K08009]
4688  
NCF2; neutrophil cytosolic factor 2 [KO:K08010]
653361  
NCF1; neutrophil cytosolic factor 1 [KO:K08011]
4689  
NCF4; neutrophil cytosolic factor 4 [KO:K08012]
695  
BTK; Bruton tyrosine kinase [KO:K07370] [EC:2.7.10.2]
7006  
TEC; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
126014  
OSCAR; osteoclast associated, immunoglobulin-like receptor [KO:K14377]
10288  
LILRB2; leukocyte immunoglobulin like receptor B2 [KO:K06512]
10859  
LILRB1; leukocyte immunoglobulin like receptor B1 [KO:K06512]
10990  
LILRB5; leukocyte immunoglobulin like receptor B5 [KO:K06512]
11006  
LILRB4; leukocyte immunoglobulin like receptor B4 [KO:K06512]
11024  
LILRA1; leukocyte immunoglobulin like receptor A1 [KO:K06512]
11025  
LILRB3; leukocyte immunoglobulin like receptor B3 [KO:K06512]
11026  
LILRA3; leukocyte immunoglobulin like receptor A3 [KO:K06512]
11027  
LILRA2; leukocyte immunoglobulin like receptor A2 [KO:K06512]
23547  
LILRA4; leukocyte immunoglobulin like receptor A4 [KO:K06512]
79168  
LILRA6; leukocyte immunoglobulin like receptor A6 [KO:K06512]
353514  
LILRA5; leukocyte immunoglobulin like receptor A5 [KO:K06512]
leukocyte immunoglobulin-like receptor subfamily B member 3; K06512 leukocyte immunoglobulin-like receptor [KO:K06512]
2209  
FCGR1A; Fc fragment of IgG receptor Ia [KO:K06498]
2212  
FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
2213  
FCGR2B; Fc fragment of IgG receptor IIb [KO:K12560]
9103  
FCGR2C; Fc fragment of IgG receptor IIc (gene/pseudogene) [KO:K16824]
2214  
FCGR3A; Fc fragment of IgG receptor IIIa [KO:K06463]
2215  
FCGR3B; Fc fragment of IgG receptor IIIb [KO:K06463]
54209  
TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
140885  
SIRPA; signal regulatory protein alpha [KO:K06551]
55423  
SIRPG; signal regulatory protein gamma [KO:K06551]
10326  
SIRPB1; signal regulatory protein beta 1 [KO:K06551]
7305  
TYROBP; TYRO protein tyrosine kinase binding protein [KO:K07992]
6850  
SYK; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
29760  
BLNK; B-cell linker [KO:K07371]
3937  
LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
5336  
PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
5530  
PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
814  
CAMK4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
1385  
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
6688  
SPI1; Spi-1 proto-oncogene [KO:K09438]
4286  
MITF; microphthalmia-associated transcription factor [KO:K09455]
1513  
CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
54  
ACP5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
799  
CALCR; calcitonin receptor [KO:K04576]
3690  
ITGB3; integrin subunit beta 3 [KO:K06493]
5468  
PPARG; peroxisome proliferator activated receptor gamma [KO:K08530]
3454  
IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
3455  
IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
3716  
JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
7297  
TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
6773  
STAT2; signal transducer and activator of transcription 2 [KO:K11221]
10379  
IRF9; interferon regulatory factor 9 [KO:K04693]
8651  
SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
9021  
SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
9846  
GAB2; GRB2 associated binding protein 2 [KO:K08091]
2274  
FHL2; four and a half LIM domains 2 [KO:K14380]
1540  
CYLD; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
8878  
SQSTM1; sequestosome 1 [KO:K14381]
Compound
C00027  
Hydrogen peroxide
C00076  
Calcium cation
C01245  
D-myo-Inositol 1,4,5-trisphosphate
Reference
  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)
Reference
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
Reference
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
Reference
  Authors
Caetano-Lopes J, Canhao H, Fonseca JE
  Title
Osteoimmunology--the hidden immune regulation of bone.
  Journal
Autoimmun Rev 8:250-5 (2009)
Reference
  Authors
Lorenzo J, Horowitz M, Choi Y
  Title
Osteoimmunology: interactions of the bone and immune system.
  Journal
Endocr Rev 29:403-40 (2008)
Reference
  Authors
David JP
  Title
Osteoimmunology: a view from the bone.
  Journal
Adv Immunol 95:149-65 (2007)
Reference
  Authors
Jimi E, Ghosh S
  Title
Role of nuclear factor-kappaB in the immune system and bone.
  Journal
Immunol Rev 208:80-7 (2005)
Reference
  Authors
Boyle WJ, Simonet WS, Lacey DL
  Title
Osteoclast differentiation and activation.
  Journal
Nature 423:337-42 (2003)
Reference
  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)
Reference
  Authors
Baron R
  Title
Arming the osteoclast.
  Journal
Nat Med 10:458-60 (2004)
Reference
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Takayanagi H, Kim S, Koga T, Taniguchi T
  Title
Stat1-mediated cytoplasmic attenuation in osteoimmunology.
  Journal
J Cell Biochem 94:232-40 (2005)
Reference
  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)
Reference
  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)
Reference
  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)
KO pathway
 

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