KEGG   PATHWAY: hsa04380
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 and regeneration
Pathway map
hsa04380  Osteoclast differentiation
hsa04380

Drug
D00107  Tacrolimus (USP/INN)
D00184  Cyclosporine (USP)
D00249  Calcitonin salmon (JP18/USP/INN)
D00742  Etanercept (USAN/INN)
D01146  Iguratimod (JAN/INN)
D02597  Adalimumab (USAN/INN)
D02598  Infliximab (USAN/INN)
D03287  Elcatonin (JP18/INN)
D03441  Certolizumab pegol (USAN/INN)
D03684  Denosumab (USAN)
D03736  Doramapimod (USAN/INN)
D04358  Golimumab (USAN/INN)
D05480  Pimecrolimus (JAN/USAN/INN)
D06634  Relacatib (USAN/INN)
D08556  Tacrolimus (INN)
D08955  Odanacatib (JAN/USAN)
D08963  Pamapimod (INN/USAN)
D09033  Voclosporin (JAN/USAN/INN)
D09386  Talmapimod (USAN/INN)
D09602  Dilmapimod (USAN/INN)
D09603  Dilmapimod tosylate (USAN)
D10308  Baricitinib (JAN/USAN/INN)
D11234  Emactuzumab (USAN/INN)
D11270  Pexidartinib (USAN/INN)
D11271  Pexidartinib hydrochloride (JAN/USAN)
D11778  Daxdilimab (USAN)
D11817  Deucravacitinib (JAN/USAN)
D12158  Elsubrutinib (USAN/INN)
D12238  Vimseltinib (USAN/INN)
D12342  Anzurstobart (USAN)
D12383  Edralbrutinib (USAN/INN)
D12467  Evobrutinib (USAN/INN)
D12504  Nemtabrutinib (USAN/INN)
D12725  Lomedeucitinib (USAN)
D12775  Polzastobart (USAN/INN)
D12826  Maplirpacept (USAN/INN)
D12996  Iluzanebart (USAN/INN)
D13123  Envudeucitinib (USAN/INN)
D13166  Vimseltinib dihydrate
Other DBs
GO: 0030316
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; RAC-gamma serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
102725035  [KO:K06512]
10288  LILRB2; leukocyte immunoglobulin-like receptor subfamily B member 2 isoform 2 precursor [KO:K06512]
10326  SIRPB1; signal-regulatory protein beta-1 isoform 3 precursor [KO:K06551]
10379  IRF9; interferon regulatory factor 9 isoform 2 [KO:K04693]
10454  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 isoform alpha [KO:K04403]
107987425  [KO:K06512]
107987441  [KO:K06512]
107987462  [KO:K06512]
10859  LILRB1; leukocyte immunoglobulin-like receptor subfamily B member 1 isoform 2 precursor [KO:K06512]
10990  LILRB5; leukocyte immunoglobulin-like receptor subfamily B member 5 isoform 2 precursor [KO:K06512]
11006  LILRB4; leukocyte immunoglobulin-like receptor subfamily B member 4 isoform 4 precursor [KO:K06512]
110117499  P3R3URF-PIK3R3; LOC110117498-PIK3R3 readthrough [KO:K02649]
11024  LILRA1; leukocyte immunoglobulin-like receptor subfamily A member 1 isoform 1 precursor [KO:K06512]
11025  LILRB3; leukocyte immunoglobulin-like receptor subfamily B member 3 isoform 1 precursor [KO:K06512]
11026  LILRA3; leukocyte immunoglobulin-like receptor subfamily A member 3 isoform 1 precursor [KO:K06512]
11027  LILRA2; leukocyte immunoglobulin-like receptor subfamily A member 2 isoform a precursor [KO:K06512]
112268336  [KO:K06512]
112268337  [KO:K06512]
112268340  [KO:K06512]
1147  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1 [KO:K04467] [EC:2.7.11.10]
126014  OSCAR; osteoclast-associated immunoglobulin-like receptor isoform 6 precursor [KO:K14377]
1385  CREB1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
140885  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform 1 precursor [KO:K06551]
1432  MAPK14; mitogen-activated protein kinase 14 isoform 2 [KO:K04441] [EC:2.7.11.24]
1435  CSF1; macrophage colony-stimulating factor 1 isoform a precursor [KO:K05453]
1436  CSF1R; macrophage colony-stimulating factor 1 receptor isoform a precursor [KO:K05090] [EC:2.7.10.1]
1513  CTSK; cathepsin K preproprotein [KO:K01371] [EC:3.4.22.38]
1535  CYBA; cytochrome b-245 light chain [KO:K08009]
1540  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform 1 [KO:K08601] [EC:3.4.19.12]
169200  TMEM64; transmembrane protein 64 isoform 1 [KO:K26770]
207  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
208  AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
2209  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform 2 precursor [KO:K06498]
2212  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform 1 precursor [KO:K06472]
2213  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b isoform 1 precursor [KO:K12560]
2214  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor [KO:K06463]
2215  FCGR3B; low affinity immunoglobulin gamma Fc region receptor III-B isoform 2 precursor [KO:K06463]
2274  FHL2; four and a half LIM domains protein 2 isoform a [KO:K14380]
23118  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform a [KO:K04404]
2353  FOS; protein c-Fos [KO:K04379]
2354  FOSB; protein FosB isoform 1 [KO:K09029]
23547  LILRA4; leukocyte immunoglobulin-like receptor subfamily A member 4 precursor [KO:K06512]
2355  FOSL2; fos-related antigen 2 [KO:K09030]
2534  FYN; tyrosine-protein kinase Fyn isoform a [KO:K05703] [EC:2.7.10.2]
27035  NOX1; NADPH oxidase 1 isoform 1 [KO:K08008]
2885  GRB2; growth factor receptor-bound protein 2 isoform 1 [KO:K04364]
29760  BLNK; B-cell linker protein isoform 1 [KO:K07371]
3454  IFNAR1; interferon alpha/beta receptor 1 isoform 2 precursor [KO:K05130]
3455  IFNAR2; interferon alpha/beta receptor 2 isoform a precursor [KO:K05131]
3456  IFNB1; interferon beta precursor [KO:K05415]
3458  IFNG; interferon gamma precursor [KO:K04687]
3459  IFNGR1; interferon gamma receptor 1 isoform 1 precursor [KO:K05132]
3460  IFNGR2; interferon gamma receptor 2 isoform 2 precursor [KO:K05133]
353514  LILRA5; leukocyte immunoglobulin-like receptor subfamily A member 5 isoform 1 precursor [KO:K06512]
3551  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1 [KO:K07209] [EC:2.7.11.10]
3552  IL1A; interleukin-1 alpha precursor [KO:K04383]
3553  IL1B; interleukin-1 beta proprotein [KO:K04519]
3554  IL1R1; interleukin-1 receptor type 1 isoform 1 precursor [KO:K04386]
3690  ITGB3; integrin beta-3 precursor [KO:K06493]
3708  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960]
3716  JAK1; tyrosine-protein kinase JAK1 isoform 1 [KO:K11217] [EC:2.7.10.2]
3725  JUN; transcription factor Jun [KO:K04448]
3726  JUNB; transcription factor JunB [KO:K09028]
3727  JUND; transcription factor JunD isoform JunD-FL [KO:K04449]
3932  LCK; tyrosine-protein kinase Lck isoform a [KO:K05856] [EC:2.7.10.2]
3937  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
4286  MITF; microphthalmia-associated transcription factor isoform 9 [KO:K09455]
4688  NCF2; neutrophil cytosol factor 2 isoform 1 [KO:K08010]
4689  NCF4; neutrophil cytosol factor 4 isoform 1 [KO:K08012]
4772  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform F [KO:K04446]
4773  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332]
4790  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein [KO:K02580]
4791  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform a [KO:K04469]
4792  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
487  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform b [KO:K05853] [EC:7.2.2.10]
488  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853] [EC:7.2.2.10]
489  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform a [KO:K05853] [EC:7.2.2.10]
4982  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B precursor [KO:K05148]
5290  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649]
5296  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
5336  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
54  ACP5; tartrate-resistant acid phosphatase type 5 precursor [KO:K14379] [EC:3.1.3.2]
54209  TREM2; triggering receptor expressed on myeloid cells 2 isoform 1 precursor [KO:K14378]
5468  PPARG; peroxisome proliferator-activated receptor gamma isoform 2 [KO:K08530]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform 1 [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform b [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform 2 [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
5535  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
55423  SIRPG; signal-regulatory protein gamma isoform 1 precursor [KO:K06551]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 isoform 1 [KO:K04371] [EC:2.7.11.24]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
5604  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368] [EC:2.7.12.2]
5608  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform 1 [KO:K04433] [EC:2.7.12.2]
5609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform 3 [KO:K04431] [EC:2.7.12.2]
5879  RAC1; ras-related C3 botulinum toxin substrate 1 isoform Rac1 [KO:K04392]
5970  RELA; transcription factor p65 isoform 1 [KO:K04735]
5971  RELB; transcription factor RelB isoform 1 [KO:K09253]
6300  MAPK12; mitogen-activated protein kinase 12 isoform 1 [KO:K04441] [EC:2.7.11.24]
653361  NCF1; neutrophil cytosol factor 1 [KO:K08011]
6688  SPI1; transcription factor PU.1 isoform 2 [KO:K09438]
6772  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform alpha [KO:K11220]
6773  STAT2; signal transducer and activator of transcription 2 isoform 1 [KO:K11221]
6850  SYK; tyrosine-protein kinase SYK isoform Syk(L) [KO:K05855] [EC:2.7.10.2]
6885  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform B [KO:K04427] [EC:2.7.11.25]
695  BTK; tyrosine-protein kinase BTK isoform 1 [KO:K07370] [EC:2.7.10.2]
7006  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
7040  TGFB1; transforming growth factor beta-1 proprotein preproprotein [KO:K13375]
7042  TGFB2; transforming growth factor beta-2 proprotein isoform 2 preproprotein [KO:K13376]
7046  TGFBR1; TGF-beta receptor type-1 isoform 1 precursor [KO:K04674] [EC:2.7.11.30]
7048  TGFBR2; TGF-beta receptor type-2 isoform B precursor [KO:K04388] [EC:2.7.11.30]
7124  TNF; tumor necrosis factor [KO:K03156]
7132  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform 1 precursor [KO:K03158]
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]
7297  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform 2 [KO:K11219] [EC:2.7.10.2]
7305  TYROBP; TYRO protein tyrosine kinase-binding protein isoform 1 precursor [KO:K07992]
79168  LILRA6; leukocyte immunoglobulin-like receptor subfamily A member 6 isoform 1 precursor [KO:K06512]
799  CALCR; calcitonin receptor isoform 2 precursor [KO:K04576]
8061  FOSL1; fos-related antigen 1 isoform 1 [KO:K04502]
814  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform 1 [KO:K05869] [EC:2.7.11.17]
8503  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649]
8517  IKBKG; NF-kappa-B essential modulator isoform a [KO:K07210]
8600  TNFSF11; tumor necrosis factor ligand superfamily member 11 isoform 1 [KO:K05473]
8651  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
8792  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform 1 precursor [KO:K05147]
8878  SQSTM1; sequestosome-1 isoform 1 [KO:K14381]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
9103  FCGR2C; Fc gamma receptor IIc (gene/pseudogene) [KO:K16824]
9846  GAB2; GRB2-associated-binding protein 2 isoform a [KO:K08091]
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
hsa04010  MAPK signaling pathway
hsa04020  Calcium signaling pathway
hsa04064  NF-kappa B signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04630  JAK-STAT signaling pathway
KO pathway
ko04380   

  All links  
No link information was found.
DBGET integrated database retrieval system