SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

Yongxing Zhang; Yang Chen; Hangxiang Sun; Wenkan Zhang; Lingling Zhang; Hengyuan Li; Xin Huang; Jie Yang; Zhaoming Ye

doi:10.3389/fcell.2021.693079

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

Front Cell Dev Biol. 2021 Jun 24:9:693079. doi: 10.3389/fcell.2021.693079. eCollection 2021.

Authors

Yongxing Zhang^{1

2

3}, Yang Chen⁴, Hangxiang Sun^{1

2}, Wenkan Zhang^{1

2}, Lingling Zhang^{1

2}, Hengyuan Li^{1

2}, Xin Huang^{1

2}, Jie Yang³, Zhaoming Ye^{1

2}

Affiliations

¹ Musculoskeletal Tumor Center, Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
² Institute of Orthopedic Research, Zhejiang University, Hangzhou, China.
³ Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.

Keywords: SENP3; SUMOylation; glucocorticoid-induced osteoporosis (GIOP); osteo-adipogenic differentiation; oxidative stress.