Disease relevance of OSM

• Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells [1].
• Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi's sarcoma [2].
• In conclusion, OSM is a novel regulator of human smooth muscle cell functions, acting in concert with IL-1beta, and OSM may play a role in major vascular diseases such as atherosclerosis [2].
• Oncostatin M (OSM) Cytostasis of Breast Tumor Cells: Characterization of an OSM Receptor {beta}-Specific Kernel [3].
• We detected variable levels of OSM antigen in 9 of 10 RA patient synovial fluids, but levels were not detectable in 9 of 10 osteoarthritis (OA) patient fluids [4].
• Association of OSM with kinase inhibitors such as Sts represents new therapeutic opportunities for wild-type p53 osteosarcoma [5].
• These results suggest that expression of OSMRs, which operates as a decoy receptor for OSM, is correlated with disease progression and adverse prognosis in patients with LADC [6].

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

• The gp130 subunit alone confers low-affinity binding of OSM when expressed in COS-7 cells [8].
• In contrast to its effects on normal endothelial and aortic smooth muscle cell cultures, Oncostatin M was a potent mitogen for cells derived from acquired immunodeficiency syndrome-related Kaposi's sarcoma (AIDS-KS) [9].
• Oncostatin M, a cytokine produced by activated lymphoid cells, regulates the growth and differentiation of a number of tumor and normal cells [9].
• The amino-terminal sequence of this protein was identical to the amino-terminal sequence of Oncostatin M, a glycoprotein that inhibits the growth of a variety of cancer cells [10].
• Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M [10].

Chemical compound and disease context of OSM

• 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 [11].
• More importantly, in combination with the inflammatory mediators IL-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, OSM exhibits a striking synergy, resulting in up to 50-fold higher PGE(2) production by astrocytes, astroglioma, and neuroblastoma cell lines [12].
• In order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11 [13].
• Exposure of human neuroblastoma cells (SH-SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or oncostatin-M resulted in a 30-40% decline in alpha-bungarotoxin receptors on the cells with no decrease seen in either muscarinic acetylcholine receptors or in L-type Ca2+ channels [14].
• Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis [15].

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

• In particular, OSM strongly activated the c-Jun NH(2)-terminal kinase (JNK) serine/threonine kinase and downstream components, including activating transcription factor (ATF)/cyclic AMP-responsive element binding protein family member, ATF3 [3].
• Our results demonstrate that both LIF and OSM cause tyrosine phosphorylation and activation of the gp130.LIFR combination, but the gp130.OSMRbeta complex is activated by OSM only [21].
• Electrophoretic mobility shift assay revealed that OSM stimulated AP-1-DNA binding, which was also abolished by PD 98059, fludarabine, and piceatannol [22].
• When positions Val-189/Tyr-190 and Phe-191/Val-192 were alanine-substituted, Scatchard analyses indicated a complete abrogation of OSM binding to both type receptors [23].
• Reporter gene activity was measured after treatment with androgen and/or OSM in the absence or presence of antiandrogens or protein kinase inhibitors [24].

Physical interactions of OSM

• Interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor also induced Stat complexes more selectively and to a lesser magnitude than oncostatin M [25].
• Oncostatin M binds the high-affinity leukemia inhibitory factor receptor [26].
• Therefore, we conclude that the 150-kDa OM binding protein previously characterized in a variety of cell lines is gp130 [27].
• Moreover, titration of sgp130 with OM inhibits the formation of a ternary complex comprising IL-6, sIL-6R alpha, and sgp130 [28].
• This effect is mediated by the transcription factor signal transducer and activator of transcription 3 ('STAT 3') binding to an OSM-responsive element (sequence TTCTCTTAA), and this site is distinct from, but close to, a previously reported interleukin-6-responsive element [29].

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].

References