Oncostatin M: Dual Regulator of the Skeletal and Hematopoietic Systems

Current Osteoporosis Reports, 2024 · DOI: 10.1007/s11914-023-00837-z · Published: January 10, 2024

Simple Explanation

Oncostatin M (OSM) is an inflammatory cytokine that plays a crucial role in the bone and hematopoietic systems. It is produced by cells like osteoblasts and macrophages and interacts with two receptor complexes, OSMR:GP130 and LIFR:GP130. OSM influences bone mass by stimulating osteoclast formation and promoting osteoblast commitment, affecting both bone breakdown and formation. It is also involved in the formation of heterotopic ossifications, where bone develops in unusual places like muscles after spinal cord injury. In the hematopoietic system, OSM regulates the proliferation of stem and progenitor cells in the bone marrow, impacting the production of blood cells. It also acts as a regulator of hematopoietic stem cell mobilization, a process used in stem cell transplantation.

Study Duration

Not specified

Participants

Human and mice

Evidence Level

Review

Key Findings

1
OSM regulates bone mass by stimulating osteoclast formation and promoting osteoblast commitment through the OSMR receptor.
2
OSM produced by macrophages is an important inducer of neurogenic heterotopic ossifications in peri-articular muscles following spinal cord injury.
3
OSM produced by neutrophils in the bone marrow induces hematopoietic stem and progenitor cell proliferation in an indirect manner.

Research Summary

OSM plays unique roles in regulating the maintenance and regeneration of bone, hematopoietic stem and progenitor cells, inflammation, and skeletal muscles. Dysregulated OSM production can lead to bone pathologies, defective muscle repair and formation of heterotopic ossifications in injured muscles, suboptimal mobilization of hematopoietic stem cells, exacerbated inflammatory responses, and anti-tumoral immunity. Ongoing research will establish whether neutralizing antibodies or cytokine traps may be useful to correct pathologies associated with excessive OSM production.

Practical Implications

Therapeutic Potential

Neutralizing OSM could be a therapeutic strategy for diseases characterized by excessive OSM production, such as bone pathologies and mobilopathy.

Targeted Therapies

Understanding the specific signaling pathways of OSM through OSMR and LIFR could lead to more targeted therapies for bone and hematopoietic disorders.

Improved HSC Mobilization

Neutralizing OSM may represent a new strategy to enhance HSC mobilization, particularly in donors who mobilize poorly.

Study Limitations

1
Most experiments have been performed on mice with germinal deletion of either Osm or Osmr genes.
2
The nuances in OSM and OSMR biology remain poorly understood.
3
Cell-specific conditional deletion of Osm and Osmr genes will enable identification of the key cellular sources.

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