KEGG   PATHWAY: rno04380
Entry
rno04380                    Pathway                                
Name
Osteoclast differentiation - Rattus norvegicus (rat)
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
rno04380  Osteoclast differentiation
rno04380

Other DBs
GO: 0030316
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100360880  Fosb; protein FosB [KO:K09029]
100360982  Relb; RELB proto-oncogene, NF-kB subunit [KO:K09253]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100361818  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446]
100912456  Lilrb1; leukocyte immunoglobulin-like receptor subfamily B member 3-like isoform X1 [KO:K06512]
113894  Sqstm1; sequestosome-1 isoform 1 [KO:K14381]
114243  Nox1; NADPH oxidase 1 [KO:K08008]
114495  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
114553  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
116506  Calcr; calcitonin receptor isoform 1b precursor [KO:K04576]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116591  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor III isoform 1 [KO:K06463]
116601  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
117516  Tnfsf11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
120098270  [KO:K26770]
134481532  [KO:K06472]
134484121  [KO:K00922] [EC:2.7.1.153]
134485274  [KO:K06512]
155918  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24481  Ifnb1; interferon beta precursor [KO:K05415]
24493  Il1a; interleukin-1 alpha [KO:K04383]
24494  Il1b; interleukin-1 beta [KO:K04519]
24516  Jun; transcription factor Jun [KO:K04448]
24517  Junb; transcription factor JunB [KO:K09028]
24518  Jund; transcription factor JunD isoform JunD-FL [KO:K04449]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
24835  Tnf; tumor necrosis factor [KO:K03156]
25050  Camk4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
25094  Mitf; microphthalmia-associated transcription factor isoform 1 [KO:K09455]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
25150  Fyn; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
25155  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
252971  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
25341  Tnfrsf11b; tumor necrosis factor receptor superfamily member 11B precursor [KO:K05148]
25391  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
25445  Fosl1; fos-related antigen 1 [KO:K04502]
25446  Fosl2; fos-related antigen 2 isoform 1 [KO:K09030]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
25528  Sirpa; tyrosine-protein phosphatase non-receptor type substrate 1 precursor [KO:K06551]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
25663  Il1r1; interleukin-1 receptor type 1 precursor [KO:K04386]
25664  Pparg; peroxisome proliferator-activated receptor gamma isoform 1 [KO:K08530]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
25712  Ifng; interferon gamma precursor [KO:K04687]
25732  Acp5; tartrate-resistant acid phosphatase type 5 isoform 2 precursor [KO:K14379] [EC:3.1.3.2]
288264  Ifnar1; interferon alpha/beta receptor 1 isoform 1 precursor [KO:K05130]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
289211  Fcgr2b; low affinity immunoglobulin gamma Fc region receptor II [KO:K12560]
29175  Ctsk; cathepsin K precursor [KO:K01371] [EC:3.4.22.38]
292537  Oscar; osteoclast-associated immunoglobulin-like receptor precursor [KO:K14377]
292594  Lilrb4; leukocyte immunoglobulin like receptor B4 isoform 3 precursor [KO:K06512]
29302  Itgb3; integrin beta-3 precursor [KO:K06493]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
295279  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
29591  Tgfbr1; TGF-beta receptor type-1 precursor [KO:K04674] [EC:2.7.11.30]
29693  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853] [EC:7.2.2.10]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
301227  Trem2; triggering receptor expressed on myeloid cells 2 precursor [KO:K14378]
304966  Fcgr3a; low affinity immunoglobulin gamma Fc region receptor III-A precursor [KO:K06463]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
307403  Csf1r; macrophage colony-stimulating factor 1 receptor precursor [KO:K05090] [EC:2.7.10.1]
308267  Tab2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
308350  Lilrb3; leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X6 [KO:K06512]
309165  Rela; transcription factor p65 [KO:K04735]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
309452  Nfkb2; nuclear factor NF-kappa-B p100 subunit [KO:K04469]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
311658  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
311786  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
312937  Cyld; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
313050  Lck; proto-oncogene tyrosine-protein kinase LCK [KO:K05856] [EC:2.7.10.2]
313121  Map3k7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
314322  Fos; protein c-Fos [KO:K04379]
315139  Tab1; TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
360640  Map3k14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
361493  Pira2; paired-Ig-like receptor A2 precursor [KO:K06512]
361537  Tyrobp; TYRO protein tyrosine kinase-binding protein precursor [KO:K07992]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431] [EC:2.7.12.2]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
364018  Ncf2; neutrophil cytosol factor 2 [KO:K08010]
366126  Spi1; transcription factor PU.1 [KO:K09438]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
367901  Btk; tyrosine-protein kinase BTK [KO:K07370] [EC:2.7.10.2]
498206  Tnfrsf11a; tumor necrosis factor receptor superfamily member 11A precursor [KO:K05147]
498276  Fcgr2al1; Fc gamma receptor 2A like 1 [KO:K06472]
499356  Blnk; B-cell linker protein [KO:K07371]
500904  Ncf4; neutrophil cytosol factor 4 [KO:K08012]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
59086  Tgfb1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
63839  Fhl2; four and a half LIM domains protein 2 [KO:K14380]
65146  Lilrb2; neutrophil immunoglobulin-like receptor 1 [KO:K06512]
683463  Pirb; leukocyte immunoglobulin-like receptor subfamily B member 3A precursor [KO:K06512]
686326  Ifnar2; interferon alpha and beta receptor subunit 2 isoform 1 precursor [KO:K05131]
689176  Tmem64; transmembrane protein 64 [KO:K26770]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
690906  Lilrc2; leukocyte immunoglobulin-like receptor, subfamily C, member 2 [KO:K06512]
691533  Lilra5; leukocyte immunoglobulin-like receptor subfamily A member 5 precursor [KO:K06512]
78965  Csf1; macrophage colony-stimulating factor 1 precursor [KO:K05453]
79129  Cyba; cytochrome b-245 light chain [KO:K08009]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
81809  Tgfb2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
81810  Tgfbr2; TGF-beta receptor type-2 precursor [KO:K04388] [EC:2.7.11.30]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
84477  Gab2; GRB2-associated-binding protein 2 [KO:K08091]
84492  Tec; tyrosine-protein kinase Tec [KO:K07364] [EC:2.7.10.2]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
89829  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
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
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04064  NF-kappa B signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04630  JAK-STAT signaling pathway
KO pathway
ko04380   

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