ESPEYB16 15 Editorsߣ Choice (1) (18 abstracts)
15.15. Irisin mediates effects on bone and fat via [alpha]V integrin receptors
Kim H , Wrann CD , Jedrychowski M , Vidoni S , Kitase Y , Nagano K , Zhou C , Chou J , Parkman VA , Novick SJ , Strutzenberg TS , Pascal BD , Le PT , Brooks DJ , Roche AM , Gerber KK , Mattheis L , Chen W , Tu H , Bouxsein ML , Griffin PR , Baron R , Rosen CJ , Bonewald LF & Spiegelman BM
To read the full abstract: Cell. 2018 Dec 13;175(7):1756–1768.e17.
Irisin, a cytokine secreted by muscle during exercise, effects bone resorption and the differentiation of preadipocytes into thermogenic brown fat cells by displacing tethers between the cell and extracellular matrix molecules. Physical activity can reverse age-dependent decline in skeletal muscle, preventing osteoporosis, regenerative neurogenesis, hippocampal function, cognitive ability, and neuromuscular junction formation, and the age-dependent recession correlates with Wnt signaling pathway (1). The current study shows that these effects may be mediated by Irisin.
Irisin is a hormone that muscles release in greater amounts during exercise. It binds to bone cells, where it helps new bone cells to take the place of old ones, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in bone, adipose tissues, and also brain. These effects are consistent with the known benefits of exercise, such as strengthening bones, increasing energy expenditure, and improving cognition. This study shows that irisin binds to proteins of the αV class of integrins, which has previously been reported to contribute to bone remodeling, and identifies interacting surfaces between irisin and αV/β5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocyte survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of irisin completely blocks osteocyte osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling.
The findings show that irisin binds to specific receptors on fat tissue and on the surface of osteocytes. When applied to cultured osteocytes, irisin protected the cells against certain types of cellular damage. Mice that received irisin injections showed elevated levels of sclerostin, an important regulator of the process by which old bone cells break down and are replaced by new ones.
These and previous data suggest that irisin could be a useful target for the treatment of osteoporosis. Although irisin targets bone resorption, intermittent treatment with irisin improves bone density and strength, similar to the dual effects of PTH. There is much evidence that exercise brings improvements in mood and cognition, and irisin might mediate some of these effects in the brain.
Reference: 1. Hu S, Yang L, Wu C, Liu TY. Regulation of Wnt signaling by physical exercise in the cell biological processes of the locomotor system. Physiol Int. 2019 Mar 1;106(1):1–20.
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ESPE Yearbook of Paediatric Endocrinology
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