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

Dongdong Zhang, Chu Hyun Bae, Junghak Lee, Jiho Lee, Zeyu Jin, Myeongmo Kang, Young Suk Cho, Jeong Han Kim, Weontae Lee, Sung Kil Lim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1). Furthermore, we showed that the promotion of r-irisin on the proliferation and differentiation of osteoblast lineage cells are preferentially through aerobic glycolysis, as indicated by the enhanced abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels. Suppression of r-irisin-mediated aerobic glycolysis with Dichloroacetate blunted its anabolic effects. The favorite of the aerobic glycolysis after r-irisin treatment was then confirmed in primary calvarial cells by metabolic analysis using gas chromatography–mass spectrometry. Thus, our results suggest that the anabolic actions of r-irisin on the regulation of osteoblast lineage cells are preferentially through aerobic glycolysis, which may help to develop new irisin-based bone anabolic agents.

Original languageEnglish
Pages (from-to)150-160
Number of pages11
JournalBone
Volume114
DOIs
Publication statusPublished - 2018 Sep

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Anabolic Agents
Glycolysis
Osteoblasts
Bone and Bones
Differentiation Antigens
Osteogenesis
Skeleton
Alkaline Phosphatase
Lactic Acid
Spectrum Analysis
Skeletal Muscle
Transcription Factors
Gases
Hormones
Escherichia coli
Enzymes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Zhang, Dongdong ; Bae, Chu Hyun ; Lee, Junghak ; Lee, Jiho ; Jin, Zeyu ; Kang, Myeongmo ; Cho, Young Suk ; Kim, Jeong Han ; Lee, Weontae ; Lim, Sung Kil. / The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis. In: Bone. 2018 ; Vol. 114. pp. 150-160.
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abstract = "Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1). Furthermore, we showed that the promotion of r-irisin on the proliferation and differentiation of osteoblast lineage cells are preferentially through aerobic glycolysis, as indicated by the enhanced abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels. Suppression of r-irisin-mediated aerobic glycolysis with Dichloroacetate blunted its anabolic effects. The favorite of the aerobic glycolysis after r-irisin treatment was then confirmed in primary calvarial cells by metabolic analysis using gas chromatography–mass spectrometry. Thus, our results suggest that the anabolic actions of r-irisin on the regulation of osteoblast lineage cells are preferentially through aerobic glycolysis, which may help to develop new irisin-based bone anabolic agents.",
author = "Dongdong Zhang and Bae, {Chu Hyun} and Junghak Lee and Jiho Lee and Zeyu Jin and Myeongmo Kang and Cho, {Young Suk} and Kim, {Jeong Han} and Weontae Lee and Lim, {Sung Kil}",
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The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis. / Zhang, Dongdong; Bae, Chu Hyun; Lee, Junghak; Lee, Jiho; Jin, Zeyu; Kang, Myeongmo; Cho, Young Suk; Kim, Jeong Han; Lee, Weontae; Lim, Sung Kil.

In: Bone, Vol. 114, 09.2018, p. 150-160.

Research output: Contribution to journalArticle

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T1 - The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis

AU - Zhang, Dongdong

AU - Bae, Chu Hyun

AU - Lee, Junghak

AU - Lee, Jiho

AU - Jin, Zeyu

AU - Kang, Myeongmo

AU - Cho, Young Suk

AU - Kim, Jeong Han

AU - Lee, Weontae

AU - Lim, Sung Kil

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N2 - Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1). Furthermore, we showed that the promotion of r-irisin on the proliferation and differentiation of osteoblast lineage cells are preferentially through aerobic glycolysis, as indicated by the enhanced abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels. Suppression of r-irisin-mediated aerobic glycolysis with Dichloroacetate blunted its anabolic effects. The favorite of the aerobic glycolysis after r-irisin treatment was then confirmed in primary calvarial cells by metabolic analysis using gas chromatography–mass spectrometry. Thus, our results suggest that the anabolic actions of r-irisin on the regulation of osteoblast lineage cells are preferentially through aerobic glycolysis, which may help to develop new irisin-based bone anabolic agents.

AB - Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1). Furthermore, we showed that the promotion of r-irisin on the proliferation and differentiation of osteoblast lineage cells are preferentially through aerobic glycolysis, as indicated by the enhanced abundance of representative enzymes such as lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase kinase 1 (PDK1), together with increased lactate levels. Suppression of r-irisin-mediated aerobic glycolysis with Dichloroacetate blunted its anabolic effects. The favorite of the aerobic glycolysis after r-irisin treatment was then confirmed in primary calvarial cells by metabolic analysis using gas chromatography–mass spectrometry. Thus, our results suggest that the anabolic actions of r-irisin on the regulation of osteoblast lineage cells are preferentially through aerobic glycolysis, which may help to develop new irisin-based bone anabolic agents.

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