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Gene Review

OSM  -  oncostatin M

Homo sapiens

Synonyms: MGC20461, Oncostatin-M
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Disease relevance of OSM


Psychiatry related information on OSM

  • Taken together, these findings indicate that OSM or IL-6.sIL-6 complexes may regulate ACT expression in human astrocytes and thus directly or indirectly contribute to the pathogenesis of Alzheimer's disease [7].

High impact information on OSM


Chemical compound and disease context of OSM


Biological context of OSM

  • The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter [16].
  • Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine [16].
  • These data highlight the species-specific differences in receptor utilization and signal transduction between mouse and human OSM [17].
  • After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69+/-3% of control [2].
  • JNK/stress-activated protein kinase kinase inhibition abrogated cell morphogenesis induced by OSM, indicating an important role for this pathway in OSM specificity [3].

Anatomical context of OSM

  • The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM [16].
  • OSM-induced biological effects on breast tumor-derived cell lines were specifically mediated through the gp130/OSMRbeta complex [3].
  • OSM increased endothelial cell tubule formation and migration [18].
  • OSM was found to be produced spontaneously by synovial tissue macrophages [19].
  • Thus suggesting that OSM and sIL-6R release from infiltrating neutrophils may contribute to the temporal switch between neutrophil influx and mononuclear cell recruitment seen during acute inflammation [20].

Associations of OSM with chemical compounds


Physical interactions of OSM


Regulatory relationships of OSM

  • The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein [1].
  • OnM also activates STAT1 but not transcription of STAT1-dependent genes in HepG2 cells [30].
  • Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures [18].
  • Finally, compared with either cytokine alone, the combination of OSM and IL-1beta significantly induced VEGF production in RASF/cartilage cocultures [18].
  • OSM potentiated IL-1beta-induced MMP-1 and MMP-13 expression in normal human cartilage/RASF cocultures, resulting in a significant increase in the MMP:TIMP ratio [18].

Other interactions of OSM

  • These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture [31].
  • The D214A/F284A double mutation, however, totally impaired cellular proliferation to LIF and CT-1 and partially impaired OSM-induced proliferation with a 20-fold increase in EC50 [32].
  • They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to generate, respectively, type I and type II OSM receptors [33].
  • The information is next relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors [33].
  • Interestingly, IFN gamma activation of STAT1 is considerably more long-lived than that produced by OnM [30].

Analytical, diagnostic and therapeutic context of OSM

  • Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit [34].
  • We examined the levels of OSM in the synovial fluids of patients with arthritis by an enzyme-linked immunosorbent assay (ELISA) [4].
  • Although OSM and IL-6 induced STAT (signal transducers and activators of transcription) factors to bind a high affinity Sis-inducible element DNA probe, binding to homologous TIMP-1 promoter sequences was not detected [35].
  • In OSM/IL-1beta- stimulated cocultures, cartilage sections demonstrated significant proteoglycan depletion that was paralleled by a significant increase in GAG release in supernatants [18].
  • ELISA of cell culture supernatants and Northern blots were used to assess responses of HSF to interleukin-1alpha (IL-1alpha), OSM, and other members of the IL-6/leukemia inhibitory factor (IL-6/LIF) family of cytokines [4].


  1. Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells. Chauhan, D., Kharbanda, S.M., Ogata, A., Urashima, M., Frank, D., Malik, N., Kufe, D.W., Anderson, K.C. J. Exp. Med. (1995) [Pubmed]
  2. Oncostatin M induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells : synergy with interleukin-1beta. Bernard, C., Merval, R., Lebret, M., Delerive, P., Dusanter-Fourt, I., Lehoux, S., Créminon, C., Staels, B., Maclouf, J., Tedgui, A. Circ. Res. (1999) [Pubmed]
  3. Oncostatin M (OSM) Cytostasis of Breast Tumor Cells: Characterization of an OSM Receptor {beta}-Specific Kernel. Underhill-Day, N., Heath, J.K. Cancer Res. (2006) [Pubmed]
  4. Oncostatin M stimulates monocyte chemoattractant protein-1- and interleukin-1-induced matrix metalloproteinase-1 production by human synovial fibroblasts in vitro. Langdon, C., Leith, J., Smith, F., Richards, C.D. Arthritis Rheum. (1997) [Pubmed]
  5. Sensitization of osteosarcoma cells to apoptosis by oncostatin M depends on STAT5 and p53. Chipoy, C., Brounais, B., Trichet, V., Battaglia, S., Berreur, M., Oliver, L., Juin, P., Rédini, F., Heymann, D., Blanchard, F. Oncogene (2007) [Pubmed]
  6. Expression of short-form oncostatin M receptor as a decoy receptor in lung adenocarcinomas. Chen, D., Chu, C.Y., Chen, C.Y., Yang, H.C., Chiang, Y.Y., Lin, T.Y., Chiang, I.P., Chuang, D.Y., Yu, C.C., Chow, K.C. J. Pathol. (2008) [Pubmed]
  7. Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate alpha1-antichymotrypsin expression in human cortical astrocytes. Kordula, T., Rydel, R.E., Brigham, E.F., Horn, F., Heinrich, P.C., Travis, J. J. Biol. Chem. (1998) [Pubmed]
  8. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Gearing, D.P., Comeau, M.R., Friend, D.J., Gimpel, S.D., Thut, C.J., McGourty, J., Brasher, K.K., King, J.A., Gillis, S., Mosley, B. Science (1992) [Pubmed]
  9. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Miles, S.A., Martínez-Maza, O., Rezai, A., Magpantay, L., Kishimoto, T., Nakamura, S., Radka, S.F., Linsley, P.S. Science (1992) [Pubmed]
  10. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Nair, B.C., DeVico, A.L., Nakamura, S., Copeland, T.D., Chen, Y., Patel, A., O'Neil, T., Oroszlan, S., Gallo, R.C., Sarngadharan, M.G. Science (1992) [Pubmed]
  11. Effect of azacytidine in the release of leukemia inhibitory factor, oncostatin m, interleukin (IL)-6, and IL-11 by mononuclear cells of patients with refractory anemia. López-Karpovitch, X., Barrales-Benítez, O., Flores, M., Piedras, J. Cytokine (2002) [Pubmed]
  12. Oncostatin M enhances the expression of prostaglandin E2 and cyclooxygenase-2 in astrocytes: synergy with interleukin-1beta, tumor necrosis factor-alpha, and bacterial lipopolysaccharide. Repovic, P., Mi, K., Benveniste, E.N. Glia (2003) [Pubmed]
  13. The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells. Juge-Morineau, N., François, S., Puthier, D., Godard, A., Bataille, R., Amiot, M. Br. J. Haematol. (1995) [Pubmed]
  14. Ciliary neurotrophic factor regulates nicotinic acetylcholine receptors on human neuroblastoma cells. Halvorsen, S.W., Malek, R., Wang, X., Jiang, N. Neuropharmacology (1996) [Pubmed]
  15. Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis. Sanchez, A.L., Langdon, C.M., Akhtar, M., Lu, J., Richards, C.D., Bercik, P., McKay, D.M. J. Interferon Cytokine Res. (2003) [Pubmed]
  16. Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. Yoshimura, A., Ichihara, M., Kinjyo, I., Moriyama, M., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Hara, T., Miyajima, A. EMBO J. (1996) [Pubmed]
  17. Cloning and characterization of a specific receptor for mouse oncostatin M. Lindberg, R.A., Juan, T.S., Welcher, A.A., Sun, Y., Cupples, R., Guthrie, B., Fletcher, F.A. Mol. Cell. Biol. (1998) [Pubmed]
  18. Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Fearon, U., Mullan, R., Markham, T., Connolly, M., Sullivan, S., Poole, A.R., Fitzgerald, O., Bresnihan, B., Veale, D.J. Arthritis Rheum. (2006) [Pubmed]
  19. The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis. Okamoto, H., Yamamura, M., Morita, Y., Harada, S., Makino, H., Ota, Z. Arthritis Rheum. (1997) [Pubmed]
  20. Secretion of oncostatin M by infiltrating neutrophils: regulation of IL-6 and chemokine expression in human mesothelial cells. Hurst, S.M., McLoughlin, R.M., Monslow, J., Owens, S., Morgan, L., Fuller, G.M., Topley, N., Jones, S.A. J. Immunol. (2002) [Pubmed]
  21. Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation. Mosley, B., De Imus, C., Friend, D., Boiani, N., Thoma, B., Park, L.S., Cosman, D. J. Biol. Chem. (1996) [Pubmed]
  22. MEK/ERK and signal transducer and activator of transcription signaling pathways modulate oncostatin M-stimulated CCL2 expression in human osteoblasts through a common transcription factor. Lin, S.K., Kok, S.H., Yeh, F.T., Kuo, M.Y., Lin, C.C., Wang, C.C., Goldring, S.R., Hong, C.Y. Arthritis Rheum. (2004) [Pubmed]
  23. Identification of a gp130 cytokine receptor critical site involved in oncostatin M response. Olivier, C., Auguste, P., Chabbert, M., Lelièvre, E., Chevalier, S., Gascan, H. J. Biol. Chem. (2000) [Pubmed]
  24. Acquisition of agonistic properties of nonsteroidal antiandrogens after treatment with oncostatin M in prostate cancer cells. Godoy-Tundidor, S., Hobisch, A., Pfeil, K., Bartsch, G., Culig, Z. Clin. Cancer Res. (2002) [Pubmed]
  25. Activation of stat3 and stat1 DNA binding and transcriptional activity in human brain tumour cell lines by gp130 cytokines. Schaefer, L.K., Menter, D.G., Schaefer, T.S. Cell. Signal. (2000) [Pubmed]
  26. Oncostatin M binds the high-affinity leukemia inhibitory factor receptor. Gearing, D.P., Bruce, A.G. New Biol. (1992) [Pubmed]
  27. Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. Liu, J., Modrell, B., Aruffo, A., Marken, J.S., Taga, T., Yasukawa, K., Murakami, M., Kishimoto, T., Shoyab, M. J. Biol. Chem. (1992) [Pubmed]
  28. Oncostatin M binds directly to gp130 and behaves as interleukin-6 antagonist on a cell line expressing gp130 but lacking functional oncostatin M receptors. Sporeno, E., Paonessa, G., Salvati, A.L., Graziani, R., Delmastro, P., Ciliberto, G., Toniatti, C. J. Biol. Chem. (1994) [Pubmed]
  29. Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer. Morgan, K., Marsters, P., Morley, S., van Gent, D., Hejazi, A., Backx, M., Thorpe, E.R., Kalsheker, N. Biochem. J. (2002) [Pubmed]
  30. Activation of signal transducer and activator of transcription 1 (STAT1) is not sufficient for the induction of STAT1-dependent genes in endothelial cells. Comparison of interferon-gamma and oncostatin M. Mahboubi, K., Pober, J.S. J. Biol. Chem. (2002) [Pubmed]
  31. Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130. Nishimoto, N., Ogata, A., Shima, Y., Tani, Y., Ogawa, H., Nakagawa, M., Sugiyama, H., Yoshizaki, K., Kishimoto, T. J. Exp. Med. (1994) [Pubmed]
  32. Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor. Plun-Favreau, H., Perret, D., Diveu, C., Froger, J., Chevalier, S., Lelièvre, E., Gascan, H., Chabbert, M. J. Biol. Chem. (2003) [Pubmed]
  33. Signaling of type II oncostatin M receptor. Auguste, P., Guillet, C., Fourcin, M., Olivier, C., Veziers, J., Pouplard-Barthelaix, A., Gascan, H. J. Biol. Chem. (1997) [Pubmed]
  34. Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit. Tanaka, M., Hara, T., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Miyajima, A. Blood (1999) [Pubmed]
  35. Oncostatin M stimulates c-Fos to bind a transcriptionally responsive AP-1 element within the tissue inhibitor of metalloproteinase-1 promoter. Botelho, F.M., Edwards, D.R., Richards, C.D. J. Biol. Chem. (1998) [Pubmed]
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