KEGG   PATHWAY: mcoc04380
Entry
mcoc04380                   Pathway                                
Name
Osteoclast differentiation - Mastomys coucha (southern multimammate mouse)
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
mcoc04380  Osteoclast differentiation
mcoc04380

Other DBs
GO: 0030316
Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116067982  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116068368  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
116068447  Tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
116068714  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116068848  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116069014  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
116069482  Jund; transcription factor jun-D [KO:K04449]
116069491  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116069739  Junb; transcription factor jun-B [KO:K09028]
116069824  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
116070251  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
116070330  [KO:K08009]
116071189  Tec; tyrosine-protein kinase Tec isoform X1 [KO:K07364] [EC:2.7.10.2]
116071362  Ppp3r1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
116073359  Acp5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
116073579  Tgfbr2; TGF-beta receptor type-2 isoform X1 [KO:K04388] [EC:2.7.11.30]
116073648  Mapk6; mitogen-activated protein kinase 6 [KO:K04371] [EC:2.7.11.24]
116073764  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116073782  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
116073929  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116074547  Tnf; tumor necrosis factor isoform X1 [KO:K03156]
116074574  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
116074772  Trem2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
116075101  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116075335  Ncf4; neutrophil cytosol factor 4 [KO:K08012]
116075405  [KO:K06512]
116075406  [KO:K06512]
116075516  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116075536  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116076094  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
116076208  Ifng; interferon gamma [KO:K04687]
116076236  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
116076719  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
116076765  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116076922  Itgb3; integrin beta-3 [KO:K06493]
116077040  Sqstm1; sequestosome-1 isoform X1 [KO:K14381]
116077083  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
116077667  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
116077765  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116077791  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116078408  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
116079135  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
116079161  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116079792  Fosl2; fos-related antigen 2 [KO:K09030]
116080443  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
116080518  Fos; proto-oncogene c-Fos [KO:K04379]
116081405  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
116081769  Tnfrsf11b; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
116083721  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116084124  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116084367  Irf9; interferon regulatory factor 9 [KO:K04693]
116084439  Tnfsf11; tumor necrosis factor ligand superfamily member 11 isoform X1 [KO:K05473]
116084832  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116085165  Socs1; suppressor of cytokine signaling 1 isoform X1 [KO:K04694]
116085336  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116085641  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116086124  Ifnar2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
116086128  Ifnar1; interferon alpha/beta receptor 1 [KO:K05130]
116086134  Ifngr2; interferon gamma receptor 2 isoform X1 [KO:K05133]
116086280  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
116086957  Camk4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
116087228  Csf1r; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
116087416  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
116088003  Map3k7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
116088048  Tmem64; transmembrane protein 64 isoform X1 [KO:K26770]
116088348  Il1r1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
116088368  Fhl2; four and a half LIM domains protein 2 [KO:K14380]
116088407  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
116088513  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116088560  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
116089826  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116090459  Spi1; transcription factor PU.1 isoform X1 [KO:K09438]
116090551  Traf6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
116090915  Il1a; interleukin-1 alpha [KO:K04383]
116090916  Il1b; interleukin-1 beta [KO:K04519]
116090918  [KO:K06551]
116091445  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
116093414  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
116093601  Csf1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
116093825  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116093830  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116093973  Nox1; NADPH oxidase 1 [KO:K08008]
116094184  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
116094965  [KO:K06551]
116095058  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116095400  Ifnb1; interferon beta [KO:K05415]
116095983  Tgfbr1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
116096012  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
116096245  Jun; transcription factor AP-1 [KO:K04448]
116096295  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
116096465  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
116096709  Lck; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
116097037  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116097162  Tnfrsf11a; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
116097745  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
116097807  Ifngr1; interferon gamma receptor 1 isoform X1 [KO:K05132]
116098534  Calcr; calcitonin receptor isoform X1 [KO:K04576]
116099319  Mitf; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
116099362  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116099428  Pparg; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
116099614  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116099798  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116100338  Tyrobp; TYRO protein tyrosine kinase-binding protein [KO:K07992]
116101207  Ncf2; neutrophil cytosol factor 2 [KO:K08010]
116101516  Lilrb3; leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
116101523  Oscar; osteoclast-associated immunoglobulin-like receptor isoform X1 [KO:K14377]
116101532  [KO:K06512]
116101538  [KO:K06512]
116101747  Fosb; protein fosB isoform X1 [KO:K09029]
116101766  Relb; transcription factor RelB isoform X1 [KO:K09253]
116101857  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102583  Gab2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
116102951  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
116102969  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116103280  [KO:K12560]
116103299  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
116103308  [KO:K06463]
116103388  Fosl1; fos-related antigen 1 isoform X1 [KO:K04502]
116103403  Rela; transcription factor p65 isoform X1 [KO:K04735]
116103823  Blnk; B-cell linker protein [KO:K07371]
116103881  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
116103943  Nfkb2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116104115  [KO:K06512]
116104663  Ncf1; neutrophil cytosol factor 1 [KO:K08011]
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
mcoc04010  MAPK signaling pathway
mcoc04020  Calcium signaling pathway
mcoc04064  NF-kappa B signaling pathway
mcoc04151  PI3K-Akt signaling pathway
mcoc04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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