New rheumatoid arthritis therapy could be developed after the discovery that restricting the amount of an endogenous amino acid significantly restricts excessive formation of osteoclasts, Austrian researchers have announced.
Scientists from the MedUni Vienna, Austria, say they have identified a role for arginine in the growth of osteoclasts – multinuclear giant cells – in rheumatoid arthritis.
Writing in Nature Communications, Gernot Schabbauer, head of the Christian Doppler Laboratory for Arginine Metabolism, says the research team showed in various animal models that systemically depleting arginine in the body slows down the metabolism of these giant cells and significantly diminishes their function.
In the study, the researchers used the enzyme arginase, which lowers whole-body arginine levels, which resulted in decreased osteoclasts numbers in the bone.
Although arginine is an endogenous substance, it is also supplemented by diet and the results indicate that osteoclast formation and metabolism can be slowed down by restricting arginine in the body.
First author Julia Brunner said: “Arginine can act like a fuel for cells and essentially has several beneficial effects. However, in pathological situations, its presence can cause T-cells to overreact or lead to undesirable increases in cell numbers.”
These reactions can be restricted by the arginine-degrading enzyme arginase, which is part of the urea cycle in the liver, but also operates in immune cells.
Principal Investigator Gernot Schabbauer added: “Arginine also plays an important role in the growth and development of immune cells that operate in auto-immune diseases such as multiple sclerosis.
“Arginase is therefore not only a highly promising starting point for the development of new treatment options for rheumatoid arthritis, but it might also be important for other autoimmune diseases.”
Brunner JS, Vulliard L, Hofmann M et al. Environmental arginine controls multinuclear giant cell metabolism and formation. Nature Communications. 22 January 2020
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