The Austrian MedUni Group has defined the role that the endogenous amino acid arginine plays in the growth of osteoclasts in rheumatoid arthritis. Limiting the available amount of arginine significantly reduces the excessive formation of these harmful cells. These results were recently published in the prestigious journal Nature Communication and may serve as a basis for possible new therapeutic approaches.
Knee Joint
Rheumatoid arthritis is a common inflammatory disease of the joints that causes an increased fusion of the body’s own immune cells (macrophages) with the formation of so-called osteoclasts, which attack and destroy bone tissue. Osteoclasts require increased energy metabolism to destroy bone tissue. The results of this study now show that the increased metabolism of osteoclasts cannot be achieved without arginine.
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A group led by Gernot Schabbauer of MedUni Vienna, head of the Christian Doppler Laboratory for Arginine Metabolism, has shown in several animal models that the systemic lowering of arginine levels in the body slows down the metabolism of osteoclasts and significantly reduces their function. To achieve this, scientists used an enzyme called arginase, which reduces the level of arginine throughout the body. This has led to a reduction in the number of osteoclasts in the bones, thus reducing the damage associated with the disease.
According to lead author Julia Brunner, although arginine is an endogenous substance, it is also supplemented by diet, and the formation and metabolism of osteoclasts may be slowed by the reduction of arginine in the body.
Arginine is an amino acid that is semi-essential, that is, although it can be synthesized by the body’s own metabolic pathways, it must also be supplied through food. Arginine can serve as fuel for cells and has essentially several positive effects. However, in pathological situations, its presence can lead to an overreaction of T-cells or unwanted proliferation of cells.
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These reactions can be mitigated by using the enzyme arginase. “Arginase is part of the urea cycle in the liver, but also operates in immune cells and, hence, can act as a regulator for arginine,” explains lead researcher Gernot Schabbauer of the Institute for Vascular Biology and Thrombosis Research at MedUni Vienna. Arginine also plays an important role in the growth and development of immune cells, which act in autoimmune diseases such as multiple sclerosis. Therefore, arginase is not only a promising starting point for the development of new treatment options for rheumatoid arthritis but may also be relevant for other autoimmune diseases.
Immunologists caution, however, that the use of arginase as an effective treatment is still a long way off because giant polynuclear cells can adapt to low levels of arginine by finding other ways to generate energy for growth.
References
Brunner, J.S., Vulliard, L., Hofmann, M. et al. Environmental arginine controls multinuclear giant cell metabolism and formation. Nat Commun 11, 431 (2020). https://doi.org/10.1038/s41467-020-14285-1
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