The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis

Zhang, Dongdong; Bae, Chul Young; Lee, Junghak; Lee, Jiho; Jin, Zeyu; Kang, Myeongmo; Cho, Young Suk; Kim, Jeong‐Han; Lee, Weontae; Lim, Shin-Il

doi:10.1016/j.bone.2018.05.013

Cited by 39 publications

(30 citation statements)

References 34 publications

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“…In our study, we found that the osteogenic marker genes (Alp and ColIα1) and proliferation-related genes (CyclinA2, CyclinD1, CyclinE1, CDK2, and CDK12), ALP activity, and calcium deposition were increased after treatment with r-irisin in primary osteoblasts (Figures 2 and 3). Increasing evidence demonstrates that r-irisin effectively promoted the expressions of osteoblastic transcription regulators and osteoblast differentiation markers, ALP activity, and calcium deposition and proliferation in different osteogenic cells including calvaria primary osteoblasts [25], MC3T3-E1 cells [25,41,42], and bone marrow stromal cells (BMSCs) [24,26,27]. Our results indicated that r-irisin promoted primary osteoblast differentiation and proliferation, which is consistent with the above-reported studies.…”

Section: Discussionsupporting

confidence: 91%

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Chen

Zhang

Zhao

et al. 2020

IJMS

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Background: Irisin, a novel exercise-induced myokine, was shown to mediate beneficial effects of exercise in osteoporosis. Microgravity is a major threat to bone homeostasis of astronauts during long-term spaceflight, which results in decreased bone formation. Methods: The hind-limb unloading mice model and a random position machine are respectively used to simulate microgravity in vivo and in vitro. Results: We demonstrate that not only are bone formation and osteoblast differentiation decreased, but the expression of fibronectin type III domain-containing 5 (Fdnc5; irisin precursor) is also downregulated under simulated microgravity. Moreover, a lower dose of recombinant irisin (r-irisin) (1 nM) promotes osteogenic marker gene (alkaline phosphatase (Alp), collagen type 1 alpha-1(ColIα1)) expressions, ALP activity, and calcium deposition in primary osteoblasts, with no significant effect on osteoblast proliferation. Furthermore, r-irisin could recover the decrease in osteoblast differentiation induced by simulated microgravity. We also find that r-irisin increases β-catenin expression and partly neutralizes the decrease in β-catenin expression induced by simulated microgravity. In addition, β-catenin overexpression could also in part attenuate osteoblast differentiation reduction induced by simulated microgravity. Conclusions: The present study is the first to show that r-irisin positively regulates osteoblast differentiation under simulated microgravity through increasing β-catenin expression, which may reveal a novel mechanism, and it provides a prevention strategy for bone loss and muscle atrophy induced by microgravity.

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Section: Discussionsupporting

confidence: 91%

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Chen

Zhang

Zhao

et al. 2020

IJMS

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“…However, the results from other groupsm including ours, are the opposite. Independent research teams reported that in osteocyte‐like MLO‐Y4 cells, r‐irisin significantly downregulates scleorostin (Sost; D. Zhang et al, 2018), and irisin inhibits osteoclast differentiation (Kawao et al, 2018; Ma et al, 2018; J. Zhang, Valverde, et al, 2017). According to Colainni's in vivo study, low doses r‐irisin injection on young male mice decreases the expression of osteoblastic inhibitory genes such as Sost in tibiae (Colaianni et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Irisin deficiency disturbs bone metabolism

Zhu

Wang

et al. 2020

Journal Cellular Physiology

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Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone-like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx-Cre:FNDC5/ irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early-stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast-related gene expression and increased osteoclast-related gene expression in bone tissues, and reduced adipose tissue browning due to bone-born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gainof-function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.

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“…It is extremely interesting that the anabolic action of parathyroid hormone on bone, as demonstrated by Esen et al, was through increase of aerobic glycolysis (glucose consumption and production of lactate) via IGF-1 signalling and the same is true for irisin as anabolic agent [27,28]. The anabolic effect of irisin on bone is particularly dependent on glucose metabolism, moreover irisin plays www.journals.viamedica.pl/medical_research_journal an important role in the regulation of energy expenditure in different metabolic conditions [1,28].…”

mentioning

confidence: 96%

“…Cell to cell crosstalk in bone tissue involves not only biochemical interactions but also mechanical and electrical signaling. Bone is a metabolically active endocrine organ [1]. Metabolism of bone tissue is regulated by several factors, above all, physical exercise and hormones acting directly or indirectly on bone.…”

mentioning

confidence: 99%

“…Continuous bone remodelling essential for longitudinal growth of skeleton in children, motion, maintaining of bone mass, repairing damages and fracture healing is an energy consuming process, therefore, must be linked to energy metabolism, in particular to glucose metabolism [25,26]. The utilization of glucose by bone tissues is approximately half of that by adipose tissue and much lower than by muscles [1]. It is extremely interesting that the anabolic action of parathyroid hormone on bone, as demonstrated by Esen et al, was through increase of aerobic glycolysis (glucose consumption and production of lactate) via IGF-1 signalling and the same is true for irisin as anabolic agent [27,28].…”

mentioning

confidence: 99%

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The interplay between bone, muscle and adipose tissue — is there a role for potential new metabolic biomarker?

Biliński¹,

Paradowski²,

Sypniewska³

2019

Medical Research Journal

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Recent studies in mice and humans have shown the tight connection between bone and muscle tissues. Physical activity affects the function of osteocytes, mature bone cells, stimulating the synthesis of several hormone-like myokines in skeletal muscles. Anabolic action of physical exercise on bone is mediated by a myokine called irisin. This protein was initially assigned to regulate glucose homeostasis in humans but recently the influence of irisin on bone and adipose tissue metabolism was also demonstrated. In the human blood, irisin occurs in different forms, free or complexed, glycosylated and non-glycosylated which makes a reliable and reproducible measurement of this protein a crucial issue for the clinical interpretation of experimental findings. In humans, irisin was shown to inversely correlate with the prevalence of bone fractures. Data obtained so far suggest that irisin could be a potential target for the treatment of osteoporosis and play an important role in the bone healing process.

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The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis

Cited by 39 publications

References 34 publications

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Recombinant Irisin Prevents the Reduction of Osteoblast Differentiation Induced by Stimulated Microgravity through Increasing β-Catenin Expression

Irisin deficiency disturbs bone metabolism

The interplay between bone, muscle and adipose tissue — is there a role for potential new metabolic biomarker?

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