Entry Name Osteoclast differentiation
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 regenerationBRITE hierarchy
Pathway map Other DBs Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04364 GRB2; growth factor receptor-bound protein 2
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04379 FOS; proto-oncogene protein c-fos
K04383 IL1A; interleukin 1 alpha
K04386 IL1R1, CD121a; interleukin 1 receptor type I
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04403 MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404 MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04449 JUND; transcription factor jun-D
K04466 MAP3K14, NIK; mitogen-activated protein kinase kinase kinase 14 [EC:2.7.11.25 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04469 NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04502 FOSL1; fos-like antigen 1
K04519 IL1B; interleukin 1 beta
K04576 CALCR; calcitonin receptor
K04693 IRF9, ISGF3G, P48; interferon regulatory factor 9
K04694 SOCS1, JAB; suppressor of cytokine signaling 1
K04696 SOCS3, CIS3; suppressor of cytokine signaling 3
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05090 CSF1R, FMS, CD115; macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1 ]
K05130 IFNAR1; interferon receptor 1
K05131 IFNAR2; interferon receptor 2
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05147 TNFRSF11A, RANK, CD265; tumor necrosis factor receptor superfamily member 11A
K05148 TNFRSF11B, OPG; tumor necrosis factor receptor superfamily member 11B
K05453 CSF1, MCSF; macrophage colony-stimulating factor 1
K05473 TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K05856 LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2 ]
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K05869 CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17 ]
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06463 FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III
K06472 FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a
K06493 ITGB3, CD61; integrin beta 3
K06498 FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I
K06512 LILR, CD85; leukocyte immunoglobulin-like receptor
K06551 SIRPA_B1_G, CD172; signal-regulatory protein alpha/beta1/gamma
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07361 LCP2; lymphocyte cytosolic protein 2
K07371 BLNK; B-cell linker protein
K07992 TYROBP, DAP12; TYRO protein tyrosine kinase binding protein
K08008 NOX1, MOX1; NADPH oxidase 1
K08009 CYBA, P22PHOX; cytochrome b-245, alpha polypeptide
K08010 NCF2, P67PHOX; neutrophil cytosolic factor 2
K08011 NCF1, P47PHOX; neutrophil cytosolic factor 1
K08012 NCF4, P40PHOX; neutrophil cytosolic factor 4
K08091 GAB2; GRB2-associated-binding protein 2
K08530 NR1C3, PPARG; peroxisome proliferator-activated receptor gamma
K08601 CYLD, USLP2; ubiquitin carboxyl-terminal hydrolase CYLD [EC:3.4.19.12 ]
K09028 JUNB; transcription factor jun-B
K09030 FOSL2; fos-like antigen 2
K09253 RELB; transcription factor RelB
K09438 SPI1; transcription factor PU.1
K09455 MITF; microphthalmia-associated transcription factor
K11220 STAT1; signal transducer and activator of transcription 1
K11221 STAT2; signal transducer and activator of transcription 2
K12560 FCGR2B, CD32; low affinity immunoglobulin gamma Fc receptor II-b
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K14377 OSCAR; osteoclast-associated immunoglobulin-like receptor
K14378 TREM2; triggering receptor expressed on myeloid cells 2
K14379 ACP5; tartrate-resistant acid phosphatase type 5 [EC:3.1.3.2 ]
K14380 FHL2; four and a half LIM domains protein 2
K16824 FCGR2C, CD32; low affinity immunoglobulin gamma Fc receptor II-c
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K26770 TMEM64; transmembrane protein 64
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Takayanagi H, Sato K, Takaoka A, Taniguchi T
Title Interplay between interferon and other cytokine systems in bone metabolism.
Journal Reference Authors Takayanagi H
Title New immune connections in osteoclast formation.
Journal Reference Authors Nakashima T, Takayanagi H
Title Osteoimmunology: crosstalk between the immune and bone systems.
Journal Reference Authors Caetano-Lopes J, Canhao H, Fonseca JE
Title Osteoimmunology--the hidden immune regulation of bone.
Journal Reference Authors Lorenzo J, Horowitz M, Choi Y
Title Osteoimmunology: interactions of the bone and immune system.
Journal Reference Authors David JP
Title Osteoimmunology: a view from the bone.
Journal Reference Authors Jimi E, Ghosh S
Title Role of nuclear factor-kappaB in the immune system and bone.
Journal Reference Authors Boyle WJ, Simonet WS, Lacey DL
Title Osteoclast differentiation and activation.
Journal Reference Authors Darnay BG, Besse A, Poblenz AT, Lamothe B, Jacoby JJ
Title TRAFs in RANK signaling.
Journal Reference Authors Baron R
Title Arming the osteoclast.
Journal Reference Authors Takayanagi H
Title Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
Journal Reference Authors Krum SA, Chang J, Miranda-Carboni G, Wang CY
Title Novel functions for NFkappaB: inhibition of bone formation.
Journal Reference 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 Reference 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 Reference Authors Takayanagi H, Kim S, Koga T, Taniguchi T
Title Stat1-mediated cytoplasmic attenuation in osteoimmunology.
Journal Reference 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 Reference 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 Reference Authors Takayanagi H, Kim S, Taniguchi T
Title Signaling crosstalk between RANKL and interferons in osteoclast differentiation.
Journal Related ko04064 NF-kappa B signaling pathway
