KEGG   PATHWAY: lav04380
Entry
lav04380                    Pathway                                
Name
Osteoclast differentiation - Loxodonta africana (African savanna elephant)
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
lav04380  Osteoclast differentiation
lav04380

Other DBs
GO: 0030316
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100670704  CSF1; macrophage colony-stimulating factor 1 isoform X3 [KO:K05453]
100670956  CSF1R; macrophage colony-stimulating factor 1 receptor isoform X1 [KO:K05090] [EC:2.7.10.1]
100655474  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100657948  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100658340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100666266  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100653731  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100665045  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100675496  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100663184  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100657536  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100660187  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100663285  IFNG; interferon gamma [KO:K04687]
100665172  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100667304  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100668424  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100675032  IL1A; interleukin-1 alpha [KO:K04383]
100674746  IL1B; interleukin-1 beta [KO:K04519]
100657834  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
100677125  TNF; tumor necrosis factor isoform X2 [KO:K03156]
100672143  TNFRSF1A; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 1A [KO:K03158]
100667634  TGFB1; transforming growth factor beta-1 [KO:K13375]
100656534  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
100656286  TGFBR1; TGF-beta receptor type-1 isoform X1 [KO:K04674] [EC:2.7.11.30]
100671392  TGFBR2; TGF-beta receptor type-2 isoform X2 [KO:K04388] [EC:2.7.11.30]
100663523  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
100661891  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A [KO:K05147]
100655062  TNFRSF11B; tumor necrosis factor receptor superfamily member 11B [KO:K05148]
100670400  TRAF2; TNF receptor-associated factor 2 isoform X2 [KO:K03173] [EC:2.3.2.27]
100671471  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100666557  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
100675535  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
100661927  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
100664361  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100671064  RELB; transcription factor RelB [KO:K09253]
100657917  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X2 [KO:K04469]
100667170  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X2 [KO:K04427] [EC:2.7.11.25]
100660911  TAB1; LOW QUALITY PROTEIN: TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 [KO:K04403]
100656450  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 isoform X2 [KO:K04404]
100661492  IKBKG; LOW QUALITY PROTEIN: NF-kappa-B essential modulator [KO:K07210]
100657363  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3 [KO:K07209] [EC:2.7.11.10]
100675651  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100654730  RELA; transcription factor p65 isoform X2 [KO:K04735]
100662194  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100672662  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
100655623  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446]
100666438  IFNB1; interferon beta [KO:K05415]
100667623  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100662511  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
100673331  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100656926  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100661039  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100673238  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100654943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100674229  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100673395  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100674799  FOS; LOW QUALITY PROTEIN: proto-oncogene c-Fos [KO:K04379]
100676016  FOSB; protein fosB [KO:K09029]
100659917  FOSL2; fos-related antigen 2 [KO:K09030]
100658802  FOSL1; LOW QUALITY PROTEIN: fos-related antigen 1 [KO:K04502]
100670432  JUN; transcription factor AP-1 [KO:K04448]
100654706  JUNB; transcription factor jun-B [KO:K09028]
100664204  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100666572  cytochrome b-245 light chain [KO:K08009]
100661062  NCF2; neutrophil cytosol factor 2 isoform X2 [KO:K08010]
100673308  NCF1; LOW QUALITY PROTEIN: neutrophil cytosol factor 1 [KO:K08011]
100670564  NCF4; LOW QUALITY PROTEIN: neutrophil cytosol factor 4 [KO:K08012]
100670387  BTK; tyrosine-protein kinase BTK isoform X1 [KO:K07370] [EC:2.7.10.2]
100675216  TEC; tyrosine-protein kinase Tec isoform X3 [KO:K07364] [EC:2.7.10.2]
100661040  OSCAR; LOW QUALITY PROTEIN: osteoclast-associated immunoglobulin-like receptor [KO:K14377]
100664157  leukocyte immunoglobulin-like receptor subfamily B member 3 [KO:K06512]
100662732  leukocyte immunoglobulin-like receptor subfamily B member 3 isoform X1 [KO:K06512]
100663301  leukocyte immunoglobulin-like receptor subfamily A member 3 isoform X1 [KO:K06512]
100654974  FCGR1A; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
100654406  FCGR1B; high affinity immunoglobulin gamma Fc receptor IB isoform X1 [KO:K06498]
104846329  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform X2 [KO:K06472]
104846347  low affinity immunoglobulin gamma Fc region receptor II-b [KO:K12560]
104846346  low affinity immunoglobulin gamma Fc region receptor III-A-like [KO:K06463]
100671806  TREM2; triggering receptor expressed on myeloid cells 2 [KO:K14378]
100676425  tyrosine-protein phosphatase non-receptor type substrate 1 isoform X2 [KO:K06551]
100674055  signal-regulatory protein beta-1-like isoform X1 [KO:K06551]
100673190  signal-regulatory protein beta-1-like [KO:K06551]
100673481  signal-regulatory protein beta-1-like [KO:K06551]
100675194  signal-regulatory protein beta-1-like [KO:K06551]
100672622  signal-regulatory protein beta-1-like [KO:K06551]
100673775  signal-regulatory protein beta-1-like [KO:K06551]
100658725  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X2 [KO:K07992]
100663651  SYK; LOW QUALITY PROTEIN: tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
100671172  BLNK; LOW QUALITY PROTEIN: B-cell linker protein [KO:K07371]
100662993  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
100658990  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100665028  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100667845  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100659666  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100676453  ATP2A1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 isoform X2 [KO:K05853] [EC:7.2.2.10]
100671775  ATP2A3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 isoform X6 [KO:K05853] [EC:7.2.2.10]
100670753  ATP2A2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 [KO:K05853] [EC:7.2.2.10]
100665110  TMEM64; transmembrane protein 64 [KO:K26770]
100661626  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
100664832  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100677352  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111751572  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100668807  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100671333  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
100675162  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100673678  SPI1; transcription factor PU.1 isoform X2 [KO:K09438]
100668533  MITF; microphthalmia-associated transcription factor isoform X1 [KO:K09455]
100673950  CTSK; cathepsin K [KO:K01371] [EC:3.4.22.38]
100657934  ACP5; tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
100654576  CALCR; calcitonin receptor [KO:K04576]
100660405  ITGB3; integrin beta-3 isoform X1 [KO:K06493]
100654408  PPARG; peroxisome proliferator-activated receptor gamma isoform X1 [KO:K08530]
100667586  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
100672898  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
100655548  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100672245  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100656374  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
100673235  IRF9; interferon regulatory factor 9 isoform X2 [KO:K04693]
100664110  SOCS1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
100670741  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100663169  GAB2; GRB2-associated-binding protein 2 isoform X2 [KO:K08091]
100660113  FHL2; four and a half LIM domains protein 2 [KO:K14380]
100677482  CYLD; ubiquitin carboxyl-terminal hydrolase CYLD [KO:K08601] [EC:3.4.19.12]
100675905  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
lav04010  MAPK signaling pathway
lav04020  Calcium signaling pathway
lav04064  NF-kappa B signaling pathway
lav04151  PI3K-Akt signaling pathway
lav04630  JAK-STAT signaling pathway
KO pathway
ko04380   
LinkDB

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