Resveratrol suppresses insulin-like growth factor I-induced osteoblast migration: attenuation of the p44/p42 MAP kinase pathway

Author:

Hioki Tomoyuki12,Kawabata Tetsu13,Sakai Go13,Fujita Kazuhiko13,Kuroyanagi Gen14,Matsushima-Nishiwaki Rie1,Kim Woo15,Otsuka Takanobu3,Iida Hiroki5,Tokuda Haruhiko16,Kozawa Osamu1

Affiliation:

1. Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan

2. Department of Dermatology, Kizawa Memorial Hospital, Minokamo, Japan

3. Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

4. Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

5. Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

6. Department of Clinical Laboratory/Biobank of Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan

Abstract

Abstract Resveratrol is a natural polyphenol with beneficial antioxidant properties. It suppresses the migration of osteoblast-like MC3T3-E1 cells induced by epidermal growth factor, via SIRT1-mediated inhibition of SAPK/JNK and Akt. Moreover, insulin-like growth factor-I (IGF-I) stimulates the migration involving the pathways of p44/p42 mitogen-activated protein (MAP) kinase and Akt. Therefore, we investigated the effects of resveratrol on IGF-I-induced cell migration. Resveratrol and SRT1720, an activator of SIRT1, suppressed IGF-I-induced migration. Inauhzin, a SIRT1 inhibitor, significantly rescued the inhibition of IGF-I-induced cell migration by resveratrol. Resveratrol inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase but not Akt. SRT1720 inhibited IGF-I-induced phosphorylation of p44/p42 MAP kinase. Furthermore, PD98059, p44/p42 MAP kinase inhibitor, alone suppressed IGF-I-induced osteoblast migration, but did not affect the suppressive effect of resveratrol when administered concomitantly. These findings strongly suggest that resveratrol suppresses IGF-I-induced osteoblast migration via SIRT1 activation at least partially by attenuating the p44/p42 MAP kinase pathway.

Funder

National Center for Geriatrics and Gerontology

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

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