KEGG   PATHWAY: ko04380Help
ko04380                     Pathway                                

Osteoclast differentiation
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.
Organismal Systems; Development
BRITE hierarchy
Pathway map
ko04380  Osteoclast differentiation

Ortholog table
H00436  Osteopetrosis
H00437  Paget disease of bone
H00438  Nasu-Hakola disease
H00540  Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  Incontinentia pigmenti
H00800  Loeys-Dietz syndrome
H00882  Cocoon syndrome
H01132  Aplastic anemia
H01187  Tietz syndrome
H01240  Immune thrombocytopenia
H01593  Osteoporosis
H02042  Familial expansile osteolysis
Other DBs
BSID: 193096
GO: 0030316
K05453  macrophage colony-stimulating factor 1
K05090  macrophage colony-stimulating factor 1 receptor [EC:]
K04364  growth factor receptor-binding protein 2
K04371  mitogen-activated protein kinase 1/3 [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:]
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K11220  signal transducer and activator of transcription 1
K04383  interleukin 1 alpha
K04519  interleukin 1 beta
K04386  interleukin 1 receptor type I
K03156  tumor necrosis factor superfamily, member 2
K03158  tumor necrosis factor receptor superfamily member 1A
K13375  transforming growth factor beta-1
K13376  transforming growth factor beta-2
K04674  TGF-beta receptor type-1 [EC:]
K04388  TGF-beta receptor type-2 [EC:]
K05473  tumor necrosis factor ligand superfamily member 11
K05147  tumor necrosis factor receptor superfamily member 11A
K05148  tumor necrosis factor receptor superfamily member 11B
K03173  TNF receptor-associated factor 2 [EC:]
K03175  TNF receptor-associated factor 6 [EC:]
K05856  lymphocyte cell-specific protein tyrosine kinase [EC:]
K05703  tyrosine-protein kinase Fyn [EC:]
K04466  mitogen-activated protein kinase kinase kinase 14 [EC:]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K09253  transcription factor RelB
K04469  nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:]
K04403  TAK1-binding protein 1
K04404  TAK1-binding protein 2
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K04734  NF-kappa-B inhibitor alpha
K04735  transcription factor p65
K02580  nuclear factor NF-kappa-B p105 subunit
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K05415  interferon beta
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04433  mitogen-activated protein kinase kinase 6 [EC:]
K04441  p38 MAP kinase [EC:]
K04431  mitogen-activated protein kinase kinase 7 [EC:]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K04379  proto-oncogene protein c-fos
K09029  protein FosB
K09030  fos-like antigen 2
K04502  fos-like antigen 1
K04448  transcription factor AP-1
K04449  transcription factor jun-D
K09028  transcription factor jun-B
K04392  Ras-related C3 botulinum toxin substrate 1
K08008  NADPH oxidase 1
K08009  cytochrome b-245, alpha polypeptide
K08010  neutrophil cytosolic factor 2
K08011  neutrophil cytosolic factor 1
K08012  neutrophil cytosolic factor 4
K07370  Bruton agammaglobulinemia tyrosine kinase [EC:]
K07364  tyrosine-protein kinase Tec [EC:]
K14377  osteoclast-associated immunoglobulin-like receptor
K06512  leukocyte immunoglobulin-like receptor
K06498  high affinity immunoglobulin gamma Fc receptor I
K06472  low affinity immunoglobulin gamma Fc receptor II-a
K12560  low affinity immunoglobulin gamma Fc receptor II-b
K16824  low affinity immunoglobulin gamma Fc receptor II-c
K06463  low affinity immunoglobulin gamma Fc receptor III
K14378  triggering receptor expressed on myeloid cells 2
K06551  signal-regulatory protein alpha/beta1/gamma
K07992  TYRO protein tyrosine kinase binding protein
K05855  spleen tyrosine kinase [EC:]
K07371  B-cell linker protein
K07361  lymphocyte cytosolic protein 2
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:]
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K05869  calcium/calmodulin-dependent protein kinase IV [EC:]
K05870  cyclic AMP-responsive element-binding protein 1
K09438  transcription factor PU.1
K09455  microphthalmia-associated transcription factor
K01371  cathepsin K [EC:]
K14379  tartrate-resistant acid phosphatase type 5 [EC:]
K04576  calcitonin receptor
K06493  integrin beta 3
K08530  peroxisome proliferator-activated receptor gamma
K05130  interferon receptor 1
K05131  interferon receptor 2
K11217  Janus kinase 1 [EC:]
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:]
K11221  signal transducer and activator of transcription 2
K04693  interferon regulatory factor 9
K04694  suppressor of cytokine signaling 1
K04696  suppressor of cytokine signaling 3
K08091  growth factor receptor bound protein 2-associated protein 2
K14380  four and a half LIM domains protein 2
K08601  ubiquitin carboxyl-terminal hydrolase CYLD [EC:]
K14381  sequestosome 1
C00027  Hydrogen peroxide
C00076  Calcium cation
C01245  D-myo-Inositol 1,4,5-trisphosphate
Takayanagi H, Sato K, Takaoka A, Taniguchi T
Interplay between interferon and other cytokine systems in bone metabolism.
Immunol Rev 208:181-93 (2005)
Takayanagi H
New immune connections in osteoclast formation.
Ann N Y Acad Sci 1192:117-23 (2010)
Nakashima T, Takayanagi H
Osteoimmunology: crosstalk between the immune and bone systems.
J Clin Immunol 29:555-67 (2009)
Caetano-Lopes J, Canhao H, Fonseca JE
Osteoimmunology--the hidden immune regulation of bone.
Autoimmun Rev 8:250-5 (2009)
Lorenzo J, Horowitz M, Choi Y
Osteoimmunology: interactions of the bone and immune system.
Endocr Rev 29:403-40 (2008)
David JP
Osteoimmunology: a view from the bone.
Adv Immunol 95:149-65 (2007)
Jimi E, Ghosh S
Role of nuclear factor-kappaB in the immune system and bone.
Immunol Rev 208:80-7 (2005)
Boyle WJ, Simonet WS, Lacey DL
Osteoclast differentiation and activation.
Nature 423:337-42 (2003)
Darnay BG, Besse A, Poblenz AT, Lamothe B, Jacoby JJ
TRAFs in RANK signaling.
Adv Exp Med Biol 597:152-9 (2007)
Baron R
Arming the osteoclast.
Nat Med 10:458-60 (2004)
Takayanagi H
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
Nat Rev Immunol 7:292-304 (2007)
Krum SA, Chang J, Miranda-Carboni G, Wang CY
Novel functions for NFkappaB: inhibition of bone formation.
Nat Rev Rheumatol 6:607-11 (2010)
Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY
A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation.
Blood 106:852-9 (2005)
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
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals.
Cell 132:794-806 (2008)
Takayanagi H, Kim S, Koga T, Taniguchi T
Stat1-mediated cytoplasmic attenuation in osteoimmunology.
J Cell Biochem 94:232-40 (2005)
Jin W, Chang M, Paul EM, Babu G, Lee AJ, Reiley W, Wright A, Zhang M, You J, Sun SC
Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice.
J Clin Invest 118:1858-66 (2008)
Bai S, Kitaura H, Zhao H, Chen J, Muller JM, Schule R, Darnay B, Novack DV, Ross FP, Teitelbaum SL
FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner.
J Clin Invest 115:2742-51 (2005)
Takayanagi H, Kim S, Taniguchi T
Signaling crosstalk between RANKL and interferons in osteoclast differentiation.
Arthritis Res 4 Suppl 3:S227-32 (2002)
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