Oncostatin M (OSM) is a type of signaling protein, known as a cytokine, which facilitates communication between cells. It plays a part in various biological processes within the body. OSM’s involvement extends across both normal physiological functions and the development of certain diseases, making it a subject of scientific interest.
The Nature and Normal Functions of Oncostatin M
Oncostatin M is classified as a member of the interleukin-6 (IL-6) family of cytokines, sharing structural and functional similarities with other members like leukemia inhibitory factor (LIF). It is primarily produced by various immune cells, including activated monocytes, macrophages, T cells, dendritic cells, and neutrophils, as well as by osteoblasts. This protein has a four-alpha-helix bundle structure and is known for its stability across a range of pH levels and temperatures.
OSM exerts its effects by binding to specific receptors on the surface of target cells. There are two main receptor complexes for OSM. Upon binding, these receptor complexes initiate intracellular signaling pathways, predominantly activating the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. OSM signaling can also trigger other pathways like Ras-MAPK and PI3K-Akt.
In healthy physiological contexts, OSM contributes to several bodily functions. It plays a role in the formation and maintenance of the bone marrow niche, which is important for hematopoiesis, the process of blood cell formation. OSM influences bone metabolism by both stimulating osteoclast formation, which breaks down bone, and promoting osteoblast commitment, which forms new bone. It also regulates inflammatory responses, with the capacity to either promote or inhibit inflammation depending on the specific cell type and the surrounding molecular environment. Beyond these roles, OSM supports nerve cell growth, is involved in liver development and regeneration, and contributes to tissue remodeling processes.
Oncostatin M’s Involvement in Disease
Dysregulation of Oncostatin M (OSM) contributes to the progression of various diseases. In cancer, OSM can promote tumor growth, metastasis, and angiogenesis. It also plays a part in immune evasion. OSM’s presence is linked to poor outcomes in several cancer types, including primary liver cancers such as hepatocellular carcinoma and cholangiocarcinoma, where it influences tumor proliferation and resistance to drugs.
OSM is also implicated in chronic inflammatory conditions like rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In RA, elevated levels of OSM are found in the synovial fluid and synovium of patients. OSM derived from macrophages can act on synovial fibroblasts, activating inflammatory and tissue-destructive pathways, and promoting bone destruction and angiogenesis within the joints. This cytokine can also stimulate fibroblast-like synoviocytes to secrete pro-inflammatory cytokines, aggravating synovitis.
In inflammatory bowel disease, OSM expression increases with disease severity and is linked to anti-TNF therapy failure. OSM and its receptor are upregulated in severely inflamed colonic lesions. OSM also contributes to fibrotic diseases such as liver fibrosis, lung fibrosis, and systemic sclerosis. It promotes the deposition of collagen and other extracellular matrix components, leading to tissue scarring. OSM can induce the expression of tissue inhibitors of metalloproteinases (TIMPs), favoring matrix accumulation and contributing to the fibrotic process.
Targeting Oncostatin M in Medicine
Oncostatin M (OSM) and its signaling pathway represent potential targets for therapeutic intervention. Researchers are exploring strategies to block OSM’s activity to mitigate its effects in disease. This often involves developing molecules that can interfere with OSM’s ability to bind to its receptors or activate downstream signaling pathways.
One approach is the use of antibodies designed to bind specifically to OSM or its receptor, preventing OSM from initiating its pro-disease signals. Such targeted therapies aim to reduce inflammation, inhibit tumor growth, or lessen fibrotic tissue accumulation. In rheumatoid arthritis, for example, inhibiting OSM signaling in synovial fibroblasts is a focus for drug development to reduce inflammation and joint destruction.
Therapeutic interventions targeting OSM are also being investigated for inflammatory bowel disease, especially in patients who do not respond to conventional anti-tumor necrosis factor (TNF) therapies. Targeting OSM or its receptor could offer a more effective treatment option for these patients. In cancer, OSM-related pathways are being explored for their potential to inhibit tumor growth by modulating inflammatory responses, angiogenesis, proliferation, and metastatic characteristics.