Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature

Abstract

Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease.

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

“…Irisin has been shown to be increased in the blood of humans and mice with exercise. Irisin, working mainly through its receptor α V β 5 integrin, has been shown to have powerful effects on fat, bone, and brain tissues ( Boström et al, 2012 ; Tsourdi et al, 2022 ; Korta et al, 2019 ; Islam et al, 2021 ; Kim et al, 2018 ; Colaianni et al, 2017 ; Wrann et al, 2013 ; Xin et al, 2016 ; Wang et al, 2017 ; Bao et al, 2022 ; Zhang et al, 2022 ). With regard to bone, studies have generated complex and even contradictory results ( Erickson, 2013 ; Maak et al, 2021 ; Colaianni and Grano, 2015 ; Kim et al, 2018 ; Estell et al, 2020 ; Colaianni et al, 2014 ; Zhang et al, 2018 ).…”

“…Irisin is a recently discovered myokine generated in response to exercise when fibronectin type III domain containing protein 5 (FNDC5) is proteolytically cleaved by a yet undetermined protease ( Boström et al, 2012 ). FNDC5 is expressed in the heart, kidney, testes, brain, and other tissues; however, skeletal muscle appears to be the primary producer ( Erickson, 2013 ; Maak et al, 2021 ; Tsourdi et al, 2022 ). Cleaved irisin circulates to distant organs, such as adipose tissue where irisin increases a thermogenic gene program, including the expression of uncoupling protein 1 in a process referred to as browning.…”

Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner

“…Irisin has been shown to be increased in the blood of humans and mice with exercise. Irisin, working mainly through its receptor α V β 5 integrin, has been shown to have powerful effects on fat, bone, and brain tissues Bostrom et al (2012) ; Tsourdi et al (2022) ; Korta et al (2019) ; Islam et al (2021) ; Kim et al (2018) ; Colaianni et al (2017) ; Wrann et al (2013) ; Xin et al (2016) ; Wang et al (2017) ; Bao et al (2022) ; Zhang et al (2022) . With regard to bone, studies have generated complex and even contradictory results Erickson (2013) ; Maak et al (2021) ; Colaianni and Grano (2015) ; Kim et al (2018) ; Estell et al (2020) ; Colaianni et al (2014) ; Zhang et al (2018) .…”

“…Irisin is a recently discovered myokine generated in response to exercise when Fibronectin type III Domain Containing protein 5 (FNDC5) is proteolytically cleaved by a yet undetermined protease Bostrom et al (2012) . FNDC5 is expressed in the heart, kidney, testes, brain, and other tissues; however, skeletal muscle appears to be the primary producer Erickson (2013) ; Maak et al (2021) ; Tsourdi et al (2022) . Cleaved irisin circulates to distant organs, such as adipose tissue where irisin increases a thermogenic gene program, including the expression of uncoupling protein 1 (UCP1) in a process referred to as browning.…”

“…Aging often results in hypocalcemia and bone loss due to low vitamin D, hypoparathyroidism, genetic abnormalities, medications decreasing dietary calcium absorption, and menopause in women.Calcium deficiency can lead to osteopenia, osteoporosis, and increased fracture risk, primarily due to secondary hyperparathyroidism Kumssa et al (2015); Body et al (2016).Irisin is a recently discovered myokine generated in response to exercise when Fibronectin type III Domain Containing protein 5 (FNDC5) is proteolytically cleaved by a yet undetermined protease Bostrom et al (2012). FNDC5 is expressed in the heart, kidney, testes, brain, and other tissues; however, skeletal muscle appears to be the primary producer Erickson (2013); Maak et al (2021); Tsourdi et al (2022). Cleaved irisin circulates to distant organs, such as adipose tissue where irisin increases a thermogenic gene program, including the expression of uncoupling protein 1 (UCP1) in a process referred to as browning.…”