제1저자 장동동(내과학교실, BK21)
Bone. 2018 May 15. pii: S8756-3282(18)30201-1. doi: 10.1016/j.bone.2018.05.013. [Epub ahead of print]
The bone anabolic effects of irisin are through preferential stimulation of aerobic glycolysis.
Zhang D1, Bae C2, Lee J3, Lee J3, Jin Z4, Kang M5, Cho YS5, Kim JH3, Lee W4, Lim SK6.
1Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Division of Endocrinology & Metabolism, Department of Internal Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People''s Republic of China.2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.3Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.4Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.5Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea.6Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea; Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea. Electronic address: email@example.com.
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.