The Clinical Relevance of OSM in Inflammatory Diseases: a Comprehensive Review

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Oct 16

PMID 37841259

Authors

Cody L Wolf

Clyde Pruett

Darren Lighter

Cheryl L Jorcyk

Affiliations

Soon will be listed here.

Abstract

Oncostatin M (OSM) is a pleiotropic cytokine involved in a variety of inflammatory responses such as wound healing, liver regeneration, and bone remodeling. As a member of the interleukin-6 (IL-6) family of cytokines, OSM binds the shared receptor gp130, recruits either OSMRβ or LIFRβ, and activates a variety of signaling pathways including the JAK/STAT, MAPK, JNK, and PI3K/AKT pathways. Since its discovery in 1986, OSM has been identified as a significant contributor to a multitude of inflammatory diseases, including arthritis, inflammatory bowel disease, lung and skin disease, cardiovascular disease, and most recently, COVID-19. Additionally, OSM has also been extensively studied in the context of several cancer types including breast, cervical, ovarian, testicular, colon and gastrointestinal, brain,lung, skin, as well as other cancers. While OSM has been recognized as a significant contributor for each of these diseases, and studies have shown OSM inhibition is effective at treating or reducing symptoms, very few therapeutics have succeeded into clinical trials, and none have yet been approved by the FDA for treatment. In this review, we outline the role OSM plays in a variety of inflammatory diseases, including cancer, and outline the previous and current strategies for developing an inhibitor for OSM signaling.

Citing Articles

Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.

Ji T, Huang G, Cao Y, Gao Y, Gao X J Inflamm Res. 2025; 18:3125-3141.

PMID: 40059944 PMC: 11889408. DOI: 10.2147/JIR.S508031.

Proximity extension assay revealed novel inflammatory biomarkers for follicular development and ovarian function: a prospective controlled study combining serum and follicular fluid.

Wang C, Feng Y, Chen Y, Lin X, Li X Front Endocrinol (Lausanne). 2025; 16:1525392.

PMID: 39996063 PMC: 11847672. DOI: 10.3389/fendo.2025.1525392.

The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review.

Mori T, Nagaraj N, Surico P, Zhou W, Parmar U, DEsposito F Open Life Sci. 2025; 19(1):20221023.

PMID: 39759107 PMC: 11699559. DOI: 10.1515/biol-2022-1023.

Tryptanthrin Down-Regulates Oncostatin M by Targeting GM-CSF-Mediated PI3K-AKT-NF-κB Axis.

Han N, Park H, Ko S, Moon P Nutrients. 2024; 16(23).

PMID: 39683503 PMC: 11643981. DOI: 10.3390/nu16234109.

A targeted proteomics screen reveals serum and synovial fluid proteomic signature in patients with gout.

Huang Z, Zhong X, Zhang Y, Li X, Liu M, Huang Y Front Immunol. 2024; 15:1468810.

PMID: 39611154 PMC: 11602490. DOI: 10.3389/fimmu.2024.1468810.

References

Karimi P, Islami F, Anandasabapathy S, Freedman N, Kamangar F . Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014; 23(5):700-13. PMC: 4019373. DOI: 10.1158/1055-9965.EPI-13-1057. View

Hibi K, Goto T, Sakuraba K, Shirahata A, Saito M, Ishibashi K . Methylation of OSMR gene is frequently observed in non-invasive colorectal cancer. Anticancer Res. 2011; 31(4):1293-5. View

Linsley P, Kallestad J, Ochs V, Neubauer M . Cleavage of a hydrophilic C-terminal domain increases growth-inhibitory activity of oncostatin M. Mol Cell Biol. 1990; 10(5):1882-90. PMC: 360533. DOI: 10.1128/mcb.10.5.1882-1890.1990. View

Xia B, Chen D, Zhang J, Hu S, Jin H, Tong P . Osteoarthritis pathogenesis: a review of molecular mechanisms. Calcif Tissue Int. 2014; 95(6):495-505. PMC: 4747051. DOI: 10.1007/s00223-014-9917-9. View

Caffarel M, Coleman N . Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma. J Pathol. 2014; 232(4):386-90. PMC: 4260121. DOI: 10.1002/path.4305. View

Manojkumar S, Pradeep A, Garg G, Raju A . Gingival crevicular fluid levels of oncostatin M in periodontal conditions. Cytokine. 2010; 50(3):248-52. DOI: 10.1016/j.cyto.2010.02.002. View

Larrea E, Echeverria I, Riezu-Boj J, Aldabe R, Guembe L, Sola I . Characterization of the CD40L/Oncostatin M/Oncostatin M receptor axis as an antiviral and immunostimulatory system disrupted in chronic HCV infection. J Hepatol. 2014; 60(3):482-9. DOI: 10.1016/j.jhep.2013.10.016. View

Savarese T, Campbell C, McQuain C, Mitchell K, Guardiani R, Quesenberry P . Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas. Cytokine. 2002; 17(6):324-34. DOI: 10.1006/cyto.2002.1022. View

Winder D, Chattopadhyay A, Muralidhar B, Bauer J, English W, Zhang X . Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness. J Pathol. 2011; 225(3):448-62. DOI: 10.1002/path.2968. View

10.

Chuerduangphui J, Ekalaksananan T, Chaiyarit P, Patarapadungkit N, Chotiyano A, Kongyingyoes B . Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M. PLoS One. 2018; 13(1):e0192009. PMC: 5791990. DOI: 10.1371/journal.pone.0192009. View

11.

David E, Guihard P, Brounais B, Riet A, Charrier C, Battaglia S . Direct anti-cancer effect of oncostatin M on chondrosarcoma. Int J Cancer. 2011; 128(8):1822-35. DOI: 10.1002/ijc.25776. View

12.

Waters M, Gupta A, Mockenhaupt K, Brown L, Biswas D, Kordula T . RelB acts as a molecular switch driving chronic inflammation in glioblastoma multiforme. Oncogenesis. 2019; 8(6):37. PMC: 6541631. DOI: 10.1038/s41389-019-0146-y. View

13.

Albasanz-Puig A, Murray J, Preusch M, Coan D, Namekata M, Patel Y . Oncostatin M is expressed in atherosclerotic lesions: a role for Oncostatin M in the pathogenesis of atherosclerosis. Atherosclerosis. 2011; 216(2):292-8. DOI: 10.1016/j.atherosclerosis.2011.02.003. View

14.

Araujo A, Abaurrea A, Azcoaga P, Lopez-Velazco J, Manzano S, Rodriguez J . Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment. J Clin Invest. 2022; 132(7). PMC: 8970678. DOI: 10.1172/JCI148667. View

15.

Chipoy C, Berreur M, Couillaud S, Pradal G, Vallette F, Colombeix C . Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3. J Bone Miner Res. 2004; 19(11):1850-61. DOI: 10.1359/JBMR.040817. View

16.

Tseng P, Hoon M . Oncostatin M can sensitize sensory neurons in inflammatory pruritus. Sci Transl Med. 2021; 13(619):eabe3037. PMC: 9595590. DOI: 10.1126/scitranslmed.abe3037. View

17.

Boniface K, Diveu C, Morel F, Pedretti N, Froger J, Ravon E . Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. J Immunol. 2007; 178(7):4615-22. DOI: 10.4049/jimmunol.178.7.4615. View

18.

Alexander K, Tseng H, Fleming W, Jose B, Salga M, Kulina I . Inhibition of JAK1/2 Tyrosine Kinases Reduces Neurogenic Heterotopic Ossification After Spinal Cord Injury. Front Immunol. 2019; 10:377. PMC: 6417366. DOI: 10.3389/fimmu.2019.00377. View

19.

Persson E, Souza P, Floriano-Marcelino T, Conaway H, Henning P, Lerner U . Activation of Shc1 Allows Oncostatin M to Induce RANKL and Osteoclast Formation More Effectively Than Leukemia Inhibitory Factor. Front Immunol. 2019; 10:1164. PMC: 6547810. DOI: 10.3389/fimmu.2019.01164. View

20.

Smigiel J, Parvani J, Tamagno I, Polak K, Jackson M . Breaking the oncostatin M feed-forward loop to suppress metastasis and therapy failure. J Pathol. 2018; 245(1):6-8. DOI: 10.1002/path.5063. View