KEGG   PATHWAY: mcc04380
Entry
mcc04380                    Pathway                                
Name
Osteoclast differentiation - Macaca mulatta (rhesus monkey)
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
mcc04380  Osteoclast differentiation
mcc04380

Other DBs
GO: 0030316
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100423877  IFNGR1; interferon gamma receptor 1 precursor [KO:K05132]
100424175  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
100424418  [KO:K06512]
100428682  PPP3R1; calcineurin subunit B type 1 isoform X3 [KO:K06268]
100429193  [KO:K06512]
100429845  LILRA5; leukocyte immunoglobulin-like receptor subfamily A member 5 [KO:K06512]
106992276  [KO:K06512]
106992315  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
106992409  LILRB3; LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
106993191  FOSL1; fos-related antigen 1 [KO:K04502]
106994857  OSCAR; LOW QUALITY PROTEIN: osteoclast-associated immunoglobulin-like receptor [KO:K14377]
106995758  [KO:K06512]
114669860  NFKB2; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p100 subunit [KO:K04469]
114675335  [KO:K04388] [EC:2.7.11.30]
574112  CTSK; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
574130  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
574190  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
574207  TYROBP; TYRO protein tyrosine kinase-binding protein precursor [KO:K07992]
574214  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
574258  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
574282  IFNG; interferon gamma precursor [KO:K04687]
677689  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
692336  LILRB4; leukocyte immunoglobulin-like receptor subfamily B member 4 precursor [KO:K06512]
692337  LILRA3; leukocyte immunoglobulin-like receptor subfamily A member 3 precursor [KO:K06512]
692338  LILRA6; leukocyte immunoglobulin-like receptor subfamily A member 6 precursor [KO:K06512]
692340  LILRB1; LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 1 [KO:K06512]
692341  LILRA2; leukocyte immunoglobulin-like receptor subfamily A member 2 precursor [KO:K06512]
692342  LILRA1; leukocyte immunoglobulin-like receptor subfamily A member 1 [KO:K06512]
693650  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
693914  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
694207  NCF1; neutrophil cytosol factor 1 [KO:K08011]
695197  LILRA4; leukocyte immunoglobulin-like receptor subfamily A member 4 isoform X1 [KO:K06512]
695256  [KO:K06512]
695335  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
695537  MITF; microphthalmia-associated transcription factor [KO:K09455]
695612  NCF4; neutrophil cytosol factor 4 isoform X1 [KO:K08012]
695652  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
695826  TMEM64; transmembrane protein 64 isoform X4 [KO:K26770]
696748  [KO:K08009]
696875  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
698089  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
699489  IFNGR2; interferon gamma receptor 2 [KO:K05133]
699604  IFNAR1; interferon alpha/beta receptor 1 precursor [KO:K05130]
699726  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
699736  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
699955  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
700193  IL1A; interleukin-1 alpha precursor [KO:K04383]
700197  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
700374  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
701093  CALCR; calcitonin receptor [KO:K04576]
701237  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
701376  NOX1; NADPH oxidase 1 [KO:K08008]
701850  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
702041  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
702077  FOS; proto-oncogene c-Fos [KO:K04379]
702532  CSF1; macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
703000  BTK; tyrosine-protein kinase BTK isoform X2 [KO:K07370] [EC:2.7.10.2]
703068  FOSL2; fos-related antigen 2 [KO:K09030]
703088  TGFBR2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
703101  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
703409  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
704102  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
704363  BLNK; B-cell linker protein isoform X2 [KO:K07371]
704683  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
704701  IL1B; interleukin-1 beta precursor [KO:K04519]
705357  TEC; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
705481  SQSTM1; sequestosome-1 [KO:K14381]
706955  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
707540  TGFB2; transforming growth factor beta-2 precursor [KO:K13376]
707768  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X3 [KO:K05853] [EC:7.2.2.10]
708058  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
708233  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
708391  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
708717  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
709511  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
709773  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710077  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
710324  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
710601  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
710702  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform X3 [KO:K05853] [EC:7.2.2.10]
711115  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
711180  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
711414  IFNB1; interferon beta precursor [KO:K05415]
711512  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
711726  IL1R1; interleukin-1 receptor type 1 [KO:K04386]
712010  SPI1; transcription factor PU.1 isoform X3 [KO:K09438]
712322  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
712694  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
713222  FHL2; four and a half LIM domains protein 2 isoform X3 [KO:K14380]
714173  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
714664  FCGR1A; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
714677  RELB; transcription factor RelB isoform X1 [KO:K09253]
714689  [KO:K04469]
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
714952  TGFBR1; TGF-beta receptor type-1 isoform X2 [KO:K04674] [EC:2.7.11.30]
715052  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
715071  ACP5; tartrate-resistant acid phosphatase type 5 precursor [KO:K14379] [EC:3.1.3.2]
715335  IRF9; interferon regulatory factor 9 [KO:K04693]
715467  TNF; tumor necrosis factor [KO:K03156]
715680  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
715745  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
715782  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
715794  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
715896  FOSB; protein fosB isoform X1 [KO:K09029]
715912  [KO:K06551]
715919  RELA; transcription factor p65 isoform X1 [KO:K04735]
715954  [KO:K06551]
716034  [KO:K06551]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
716258  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
716452  JUN; transcription factor AP-1 [KO:K04448]
716907  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
717379  ITGB3; integrin beta-3 [KO:K06493]
717432  [KO:K06551]
717704  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
717755  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
717811  SIRPA; tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1 [KO:K06551]
717837  JUNB; transcription factor jun-B [KO:K09028]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
718403  [KO:K06512]
718976  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
719085  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
719740  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
719996  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a precursor [KO:K06472]
720006  FCGR3; low affinity immunoglobulin gamma Fc region receptor III isoform C precursor [KO:K06463]
720009  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b isoform 1 precursor [KO:K12560]
720182  JUND; transcription factor jun-D [KO:K04449]
722033  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
722780  [KO:K06512]
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
mcc04010  MAPK signaling pathway
mcc04020  Calcium signaling pathway
mcc04064  NF-kappa B signaling pathway
mcc04151  PI3K-Akt signaling pathway
mcc04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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