KEGG   PATHWAY: mmu04380
Entry
mmu04380                    Pathway                                
Name
Osteoclast differentiation - Mus musculus (house 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
mmu04380  Osteoclast differentiation
mmu04380

Other DBs
GO: 0030316
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
12977  Csf1; colony stimulating factor 1 (macrophage) [KO:K05453]
12978  Csf1r; colony stimulating factor 1 receptor [KO:K05090] [EC:2.7.10.1]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
15978  Ifng; interferon gamma [KO:K04687]
15979  Ifngr1; interferon gamma receptor 1 [KO:K05132]
15980  Ifngr2; interferon gamma receptor 2 [KO:K05133]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
16175  Il1a; interleukin 1 alpha [KO:K04383]
16176  Il1b; interleukin 1 beta [KO:K04519]
16177  Il1r1; interleukin 1 receptor, type I [KO:K04386]
21926  Tnf; tumor necrosis factor [KO:K03156]
21937  Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
21803  Tgfb1; transforming growth factor, beta 1 [KO:K13375]
21808  Tgfb2; transforming growth factor, beta 2 [KO:K13376]
21812  Tgfbr1; transforming growth factor, beta receptor I [KO:K04674] [EC:2.7.11.30]
21813  Tgfbr2; transforming growth factor, beta receptor II [KO:K04388] [EC:2.7.11.30]
21943  Tnfsf11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
21934  Tnfrsf11a; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
18383  Tnfrsf11b; tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) [KO:K05148]
22030  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
16818  Lck; lymphocyte protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
14360  Fyn; Fyn proto-oncogene [KO:K05703] [EC:2.7.10.2]
53859  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
19698  Relb; avian reticuloendotheliosis viral (v-rel) oncogene related B [KO:K09253]
18034  Nfkb2; nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100 [KO:K04469]
26409  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
66513  Tab1; TGF-beta activated kinase 1/MAP3K7 binding protein 1 [KO:K04403]
68652  Tab2; TGF-beta activated kinase 1/MAP3K7 binding protein 2 [KO:K04404]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
18019  Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18018  Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
15977  Ifnb1; interferon beta 1, fibroblast [KO:K05415]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26399  Map2k6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
26400  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
14282  Fosb; FBJ osteosarcoma oncogene B [KO:K09029]
14284  Fosl2; fos-like antigen 2 [KO:K09030]
14283  Fosl1; fos-like antigen 1 [KO:K04502]
16476  Jun; jun proto-oncogene [KO:K04448]
16478  Jund; jun D proto-oncogene [KO:K04449]
16477  Junb; jun B proto-oncogene [KO:K09028]
19353  Rac1; Rac family small GTPase 1 [KO:K04392]
237038  Nox1; NADPH oxidase 1 [KO:K08008]
13057  Cyba; cytochrome b-245, alpha polypeptide [KO:K08009]
17970  Ncf2; neutrophil cytosolic factor 2 [KO:K08010]
17969  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
17972  Ncf4; neutrophil cytosolic factor 4 [KO:K08012]
12229  Btk; Bruton agammaglobulinemia tyrosine kinase [KO:K07370] [EC:2.7.10.2]
21682  Tec; tec protein tyrosine kinase [KO:K07364] [EC:2.7.10.2]
232790  Oscar; osteoclast associated receptor [KO:K14377]
18722  Pira1; paired-Ig-like receptor A1 [KO:K06512]
18726  Lilra6; leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 6 [KO:K06512]
18727  Pira4; paired-Ig-like receptor A4 [KO:K06512]
18729  Pira6; paired-Ig-like receptor A6 [KO:K06512]
18733  Pirb; paired Ig-like receptor B [KO:K06512]
232801  Lilra5; leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 5 [KO:K06512]
14728  Lilrb4a; leukocyte immunoglobulin-like receptor, subfamily B, member 4A [KO:K06512]
18724  Pira11; paired-Ig-like receptor A11 [KO:K06512]
100038909  Pira12; paired-Ig-like receptor A12 [KO:K06512]
18725  Pira2; paired-Ig-like receptor A2 [KO:K06512]
100041146  Pira13; paired-Ig-like receptor A13 [KO:K06512]
18730  Pira7; paired-Ig-like receptor A7 [KO:K06512]
14727  Lilrb4b; leukocyte immunoglobulin-like receptor, subfamily B, member 4B [KO:K06512]
14129  Fcgr1; Fc receptor, IgG, high affinity I [KO:K06498]
14131  Fcgr3; Fc receptor, IgG, low affinity III [KO:K06472]
14130  Fcgr2b; Fc receptor, IgG, low affinity IIb [KO:K12560]
246256  Fcgr4; Fc receptor, IgG, low affinity IV [KO:K06463]
83433  Trem2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
19261  Sirpa; signal-regulatory protein alpha [KO:K06551]
668101  Sirpb1b; signal-regulatory protein beta 1B [KO:K06551]
100038947  Sirpb1c; signal-regulatory protein beta 1C [KO:K06551]
751864  Sirpd; signal regulatory protein delta [KO:K06551]
320832  Sirpb1a; signal-regulatory protein beta 1A [KO:K06551]
22177  Tyrobp; TYRO protein tyrosine kinase binding protein [KO:K07992]
20963  Syk; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
17060  Blnk; B cell linker [KO:K07371]
16822  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
11937  Atp2a1; ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [KO:K05853] [EC:7.2.2.10]
53313  Atp2a3; ATPase, Ca++ transporting, ubiquitous [KO:K05853] [EC:7.2.2.10]
11938  Atp2a2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:7.2.2.10]
100201  Tmem64; transmembrane protein 64 [KO:K26770]
19057  Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19055  Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19058  Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
12326  Camk4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
12912  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
20375  Spi1; Spi-1 proto-oncogene [KO:K09438]
17342  Mitf; melanogenesis associated transcription factor [KO:K09455]
13038  Ctsk; cathepsin K [KO:K01371] [EC:3.4.22.38]
11433  Acp5; acid phosphatase 5, tartrate resistant [KO:K14379] [EC:3.1.3.2]
12311  Calcr; calcitonin receptor [KO:K04576]
16416  Itgb3; integrin beta 3 [KO:K06493]
19016  Pparg; peroxisome proliferator activated receptor gamma [KO:K08530]
15975  Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]
15976  Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]
16451  Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
54721  Tyk2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
20847  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
16391  Irf9; interferon regulatory factor 9 [KO:K04693]
12703  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
12702  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
14389  Gab2; growth factor receptor bound protein 2-associated protein 2 [KO:K08091]
14200  Fhl2; four and a half LIM domains 2 [KO:K14380]
74256  Cyld; CYLD lysine 63 deubiquitinase [KO:K08601] [EC:3.4.19.12]
18412  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
mmu04010  MAPK signaling pathway
mmu04020  Calcium signaling pathway
mmu04064  NF-kappa B signaling pathway
mmu04151  PI3K-Akt signaling pathway
mmu04630  JAK-STAT signaling pathway
KO pathway
ko04380   
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