KEGG   PATHWAY: rbb04380
Entry
rbb04380                    Pathway                                
Name
Osteoclast differentiation - Rhinopithecus bieti (black snub-nosed 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
rbb04380  Osteoclast differentiation
rbb04380

Other DBs
GO: 0030316
Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108528053  CSF1; macrophage colony-stimulating factor 1 [KO:K05453]
108532049  CSF1R; macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
108537414  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108523695  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
108536070  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108544591  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
108532960  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108539355  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108535636  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108534276  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108541175  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108512498  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108539069  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108521880  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108532274  IFNG; LOW QUALITY PROTEIN: interferon gamma [KO:K04687]
108522967  IFNGR1; interferon gamma receptor 1 [KO:K05132]
108536857  IFNGR2; interferon gamma receptor 2 [KO:K05133]
108527866  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
108541808  IL1A; interleukin-1 alpha [KO:K04383]
108541809  IL1B; interleukin-1 beta [KO:K04519]
108524091  IL1R1; LOW QUALITY PROTEIN: interleukin-1 receptor type 1 [KO:K04386]
108520255  TNF; tumor necrosis factor isoform X1 [KO:K03156]
108536511  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
108536158  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
108528282  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
108512466  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
108516558  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
108514105  TNFSF11; tumor necrosis factor ligand superfamily member 11 isoform X1 [KO:K05473]
108526386  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
108536211  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
108542901  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
108535559  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
108518588  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
108512073  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
108532216  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
108535077  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108531047  RELB; transcription factor RelB [KO:K09253]
108515095  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
108539499  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
108520466  TAB1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
108536673  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
108518784  IKBKG; NF-kappa-B essential modulator [KO:K07210]
108540719  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108519636  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108543519  RELA; transcription factor p65 [KO:K04735]
108532817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
108539466  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
108525049  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
108538565  IFNB1; interferon beta [KO:K05415]
108514672  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108523215  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
108528326  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108528327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
108539403  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
108539422  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
108534524  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108537794  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
108521141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108517508  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108534930  FOS; proto-oncogene c-Fos [KO:K04379]
108531100  FOSB; protein fosB isoform X1 [KO:K09029]
108532744  FOSL2; fos-related antigen 2 [KO:K09030]
108518641  FOSL1; fos-related antigen 1 isoform X1 [KO:K04502]
108532921  JUN; transcription factor AP-1 [KO:K04448]
108539600  JUNB; LOW QUALITY PROTEIN: transcription factor jun-B [KO:K09028]
108523982  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
108515883  ras-related C3 botulinum toxin substrate 1-like isoform X1 [KO:K04392]
108521137  NOX1; NADPH oxidase 1 [KO:K08008]
108520444  cytochrome b-245 light chain [KO:K08009]
108512725  NCF2; neutrophil cytosol factor 2 [KO:K08010]
108513939  NCF1; LOW QUALITY PROTEIN: neutrophil cytosol factor 1 [KO:K08011]
108518478  NCF4; neutrophil cytosol factor 4 [KO:K08012]
108544993  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
108521066  TEC; LOW QUALITY PROTEIN: tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
108529457  OSCAR; osteoclast-associated immunoglobulin-like receptor [KO:K14377]
108521207  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 1 [KO:K06512]
108521215  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily A member 4 [KO:K06512]
108521204  leukocyte immunoglobulin-like receptor subfamily A member 2 isoform X1 [KO:K06512]
108521203  LOW QUALITY PROTEIN: uncharacterized protein LOC108521203 [KO:K06512]
108521213  LILRA5; leukocyte immunoglobulin-like receptor subfamily A member 5 isoform X1 [KO:K06512]
108518721  leukocyte immunoglobulin-like receptor subfamily B member 4 [KO:K06512]
108521226  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily A member 3 [KO:K06512]
108521205  LILRB5; LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 5 [KO:K06512]
108538696  high affinity immunoglobulin gamma Fc receptor I isoform X1 [KO:K06498]
108542586  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X1 [KO:K06472]
108542588  FCGR2B; LOW QUALITY PROTEIN: low affinity immunoglobulin gamma Fc region receptor II-b [KO:K12560]
108542585  LOW QUALITY PROTEIN: low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
108528383  TREM2; triggering receptor expressed on myeloid cells 2 isoform X1 [KO:K14378]
108544516  signal-regulatory protein beta-1-like [KO:K06551]
108544546  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X1 [KO:K06551]
108544547  signal-regulatory protein beta-1 [KO:K06551]
108544548  LOW QUALITY PROTEIN: signal-regulatory protein beta-1-like [KO:K06551]
108529973  signal-regulatory protein gamma isoform X1 [KO:K06551]
108529976  SIRPA; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
108513050  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
108516810  tyrosine-protein kinase SYK-like [KO:K05855] [EC:2.7.10.2]
108538610  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
108534511  BLNK; B-cell linker protein isoform X1 [KO:K07371]
108513605  LCP2; LOW QUALITY PROTEIN: lymphocyte cytosolic protein 2 [KO:K07361]
108539491  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108528737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
108523739  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
108516255  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
108523688  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
108520719  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X1 [KO:K05853] [EC:7.2.2.10]
108534362  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
108539840  TMEM64; transmembrane protein 64 [KO:K26770]
108542795  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
108516875  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108540785  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108537161  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
108540302  CAMK4; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
108540349  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
108516316  SPI1; transcription factor PU.1 isoform X1 [KO:K09438]
108523547  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
108533261  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
108527907  ACP5; tartrate-resistant acid phosphatase type 5 isoform X1 [KO:K14379] [EC:3.1.3.2]
108528482  CALCR; calcitonin receptor [KO:K04576]
108536294  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
108517991  PPARG; peroxisome proliferator-activated receptor gamma [KO:K08530]
108536856  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
108536852  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
108532886  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
108517816  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
108516059  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
108540930  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
108541230  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
108517203  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
108543205  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
108531552  FHL2; four and a half LIM domains protein 2 isoform X1 [KO:K14380]
108536319  CYLD; LOW QUALITY PROTEIN: ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
108523366  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
rbb04010  MAPK signaling pathway
rbb04020  Calcium signaling pathway
rbb04064  NF-kappa B signaling pathway
rbb04151  PI3K-Akt signaling pathway
rbb04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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