KEGG   PATHWAY: tmu04380
Entry
tmu04380                    Pathway                                
Name
Osteoclast differentiation - Trichechus manatus latirostris (Florida manatee)
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
tmu04380  Osteoclast differentiation
tmu04380

Other DBs
GO: 0030316
Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101357438  macrophage colony-stimulating factor 1 isoform X3 [KO:K05453]
101360266  macrophage colony-stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
101359012  growth factor receptor-bound protein 2 [KO:K04364]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101346429  interferon gamma [KO:K04687]
101345582  interferon gamma receptor 1 isoform X1 [KO:K05132]
101361970  interferon gamma receptor 2 [KO:K05133]
101357916  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101359155  interleukin-1 alpha isoform X1 [KO:K04383]
101359415  IL1B; interleukin-1 beta [KO:K04519]
101358013  interleukin-1 receptor type 1 [KO:K04386]
101342656  TNF; tumor necrosis factor [KO:K03156]
101341867  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101342543  transforming growth factor beta-1 isoform X2 [KO:K13375]
101347669  transforming growth factor beta-2 isoform X1 [KO:K13376]
101359953  TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
101354258  TGF-beta receptor type-2 isoform X4 [KO:K04388] [EC:2.7.11.30]
101342165  tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101355445  tumor necrosis factor receptor superfamily member 11A [KO:K05147]
101356713  tumor necrosis factor receptor superfamily member 11B [KO:K05148]
101354911  TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101345331  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101358037  tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
101340362  tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
101343418  mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
101341290  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101349922  transcription factor RelB [KO:K09253]
101352683  nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
101346094  mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101344618  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
101355146  TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
101347574  NF-kappa-B essential modulator isoform X1 [KO:K07210]
101351256  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101355353  NF-kappa-B inhibitor alpha [KO:K04734]
101361706  transcription factor p65 [KO:K04735]
101351866  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101355751  nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332]
101359059  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101349610  interferon beta [KO:K05415]
101343332  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101344286  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101352466  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101347350  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101361614  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101361872  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101346746  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101351734  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101351967  mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101343546  mitogen-activated protein kinase 8 isoform X4 [KO:K04440] [EC:2.7.11.24]
101357016  proto-oncogene c-Fos [KO:K04379]
101355201  protein fosB [KO:K09029]
101345204  fos-related antigen 2 [KO:K09030]
101357577  fos-related antigen 1 isoform X2 [KO:K04502]
101361653  transcription factor AP-1 [KO:K04448]
101356278  transcription factor jun-B [KO:K09028]
101356054  ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101355438  cytochrome b-245 light chain isoform X1 [KO:K08009]
101356954  neutrophil cytosol factor 2 [KO:K08010]
101343104  neutrophil cytosol factor 1 isoform X1 [KO:K08011]
101342831  neutrophil cytosol factor 4 [KO:K08012]
101356880  tyrosine-protein kinase BTK isoform X2 [KO:K07370] [EC:2.7.10.2]
101354447  LOW QUALITY PROTEIN: tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
101356139  osteoclast-associated immunoglobulin-like receptor [KO:K14377]
101357905  leukocyte immunoglobulin-like receptor subfamily A member 2 isoform X1 [KO:K06512]
111821491  LOW QUALITY PROTEIN: leukocyte immunoglobulin-like receptor subfamily B member 4 [KO:K06512]
101357143  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
101342556  LOW QUALITY PROTEIN: high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
101350744  low affinity immunoglobulin gamma Fc region receptor III-like isoform X1 [KO:K06472]
101360526  low affinity immunoglobulin gamma Fc region receptor II-b isoform X1 [KO:K12560]
101360005  low affinity immunoglobulin gamma Fc region receptor III-B-like [KO:K06463]
101360268  low affinity immunoglobulin gamma Fc region receptor III-B-like [KO:K06463]
101356227  triggering receptor expressed on myeloid cells 2 [KO:K14378]
101344271  LOW QUALITY PROTEIN: signal-regulatory protein beta-1-like [KO:K06551]
101343479  signal-regulatory protein beta-1-like [KO:K06551]
101354699  tyrosine-protein phosphatase non-receptor type substrate 1 [KO:K06551]
101346535  TYRO protein tyrosine kinase-binding protein [KO:K07992]
101351806  tyrosine-protein kinase SYK isoform X2 [KO:K05855] [EC:2.7.10.2]
101351552  B-cell linker protein isoform X1 [KO:K07371]
101357269  lymphocyte cytosolic protein 2 [KO:K07361]
101346393  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101346534  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101356404  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101354392  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101354431  sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
101353652  sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X2 [KO:K05853] [EC:7.2.2.10]
101358002  sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X1 [KO:K05853] [EC:7.2.2.10]
101340421  transmembrane protein 64 [KO:K26770]
101353424  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101357894  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101347440  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
101343394  calcineurin subunit B type 1 isoform X2 [KO:K06268]
101355330  calcineurin subunit B type 2 [KO:K06268]
101343253  calcium/calmodulin-dependent protein kinase type IV isoform X3 [KO:K05869] [EC:2.7.11.17]
101356881  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101352574  transcription factor PU.1 isoform X2 [KO:K09438]
101351135  microphthalmia-associated transcription factor isoform X2 [KO:K09455]
101349596  cathepsin K [KO:K01371] [EC:3.4.22.38]
101346745  tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
101351460  calcitonin receptor [KO:K04576]
101359355  integrin beta-3 [KO:K06493]
101356506  peroxisome proliferator-activated receptor gamma isoform X2 [KO:K08530]
101361715  interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
101354122  interferon alpha/beta receptor 2 [KO:K05131]
101346613  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101357635  non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
101348948  signal transducer and activator of transcription 2 [KO:K11221]
101354811  interferon regulatory factor 9 [KO:K04693]
101355851  suppressor of cytokine signaling 1 [KO:K04694]
101348420  suppressor of cytokine signaling 3 [KO:K04696]
101346505  GRB2-associated-binding protein 2 [KO:K08091]
101356268  four and a half LIM domains protein 2 [KO:K14380]
101340355  ubiquitin carboxyl-terminal hydrolase CYLD isoform X1 [KO:K08601] [EC:3.4.19.12]
101351010  sequestosome-1 isoform X1 [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
tmu04010  MAPK signaling pathway
tmu04020  Calcium signaling pathway
tmu04064  NF-kappa B signaling pathway
tmu04151  PI3K-Akt signaling pathway
tmu04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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