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조회39

김진만Jin-Man Kim

서울아산병원

Exp. Mol. Med., 13 March 2025 | https://doi.org/10.1038/s12276-025-01419-y VGF and the VGF-derived peptide AQEE30 stimulate osteoblastic bone formation through the C3a receptor

Sung-Ah Moon ^1,9, Jin-Man Kim ^2,9, Young-Sun Lee ², Han Jin Cho ², Young Jin Choi ², Jong Hyuk Yoon ^3,4, Dayea Kim ^3,5, Xiangguo Che ⁶, Xian Jin ⁶, In-Jeoung Baek ⁷, Seung Hun Lee ⁸, Je-Young Choi ^6,*and Jung-Min Koh ^8,*

¹Department of Medical Science, AMIST, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
²Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
³Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
⁴Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, Republic of Korea.
⁵New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea.
⁶Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Korea Mouse Phenotyping Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁷Department of Cell and Genetic Engineering, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁸Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁹These authors contributed equally: Sung-Ah Moon, Jin-Man Kim.

^*Corresponding authors: correspondence to Je-Young Choi or Jung-Min Koh

Abstract

New therapeutic targets, especially those that stimulate bone formation in cortical bone, are needed to overcome the limitations of current antiosteoporotic drugs. We previously demonstrated that factors secreted from megakaryocytes (MKs) promote bone formation. Here we conducted a proteomic analysis to identify a novel bone-forming factor from MK secretions. We revealed that Vgf, a nerve growth factor-responsive gene, and its derived active peptide AQEE30 in MK-conditioned medium play important roles in osteoblast proliferation and in vitro bone formation. In both Vgf-deficient male and female mice, the cortical bone mass was significantly decreased due to reductions in osteoblast number and bone formation activity. AQEE30 stimulated intracellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity in osteoblasts, whereas an adenylyl cyclase inhibitor blocked AQEE30-stimulated osteoblast proliferation and in vitro bone formation. Complement C3a receptor-1 (C3AR1) was expressed and interacted with AQEE30 in osteoblasts, and C3AR1 inhibition blocked all AQEE30-induced changes, including stimulated proliferation, bone formation and cAMP production, in osteoblasts. Injecting mini-PEGylated AQEE30 into calvaria increased the number of osteocalcin-positive cells and new bone formation. In conclusion, this study reveals a novel role of VGF in bone formation, particularly in cortical bone, and shows that AQEE30, a VGF-derived peptide, mediates this role by activating cAMP–PKA signaling via the C3AR1 receptor in osteoblasts.

논문정보

형식Research article
게재일2025년 03월 (BRIC 등록일 2025-03-14)
연구진국내 연구진
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