Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of cytokines, is involved in diverse inflammatory responses such as wound healing, liver regeneration, and bone remodeling. It binds the shared receptor gp130, recruits either OSMRβ or LIFRβ, and activates signaling pathways like JAK/STAT, MAPK, JNK, and PI3K/AKT [1,2].

In cancer-associated cachexia, OSM overexpression in mice causes muscle wasting, while muscle-specific deletion of the OSM receptor (OSMR) and neutralization of circulating OSM preserve muscle mass and function in tumor-bearing mice, indicating OSM/OSMR signaling drives muscle atrophy [3]. In pressure-overload induced cardiac hypertrophy, OSMR-knockout (OSMR-KO) mice show aggravated cardiac hypertrophy, fibrotic remodelling, and cardiac dysfunction. The loss of OSMR activates OSM/LIFR/STAT3 signalling and promotes a pro-resolving macrophage phenotype that exacerbates inflammation and impairs cardiac repair [4].

In conclusion, OSM is a pleiotropic cytokine with a significant role in multiple biological processes and diseases. Gene knockout models, like the OSMR-KO mouse, have revealed its functions in muscle wasting associated with cancer and in cardiac hypertrophy, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Wolf, Cody L, Pruett, Clyde, Lighter, Darren, Jorcyk, Cheryl L. 2023. The clinical relevance of OSM in inflammatory diseases: a comprehensive review. In Frontiers in immunology, 14, 1239732. doi:10.3389/fimmu.2023.1239732. https://pubmed.ncbi.nlm.nih.gov/37841259/

2. Lantieri, Francesca, Bachetti, Tiziana. 2022. OSM/OSMR and Interleukin 6 Family Cytokines in Physiological and Pathological Condition. In International journal of molecular sciences, 23, . doi:10.3390/ijms231911096. https://pubmed.ncbi.nlm.nih.gov/36232392/

3. Domaniku-Waraich, Aylin, Agca, Samet, Toledo, Batu, Kashgari, Aynur Erkin, Kir, Serkan. 2024. Oncostatin M signaling drives cancer-associated skeletal muscle wasting. In Cell reports. Medicine, 5, 101498. doi:10.1016/j.xcrm.2024.101498. https://pubmed.ncbi.nlm.nih.gov/38569555/

4. Feng, Yizhou, Yuan, Yuan, Xia, Hongxia, Shen, Difei, Tang, Qizhu. 2023. OSMR deficiency aggravates pressure overload-induced cardiac hypertrophy by modulating macrophages and OSM/LIFR/STAT3 signalling. In Journal of translational medicine, 21, 290. doi:10.1186/s12967-023-04163-x. https://pubmed.ncbi.nlm.nih.gov/37120549/