J Appl Biomed 22:197-207, 2024 | DOI: 10.32725/jab.2024.021

Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling

Yu-Cong Zou^{1, *}, Kai Gao², Bao-Tao Cao², Xiao-Li He², Wei Zheng², Xiao-Fei Wang², Yu-Fu Li², Feng Li², Hua-Jun Wang^{3, *}

¹ Zhuhai Hospital of Integrated Traditional Chinese & Western Medicine, Department of Rehabilitation, Zhuhai 519020, China

² Third Hospital of Shijiazhuang, Department of Orthopedic Surgery, HeBei Province 510000, China

³ Jinan University, The First Affiliated Hospital, Department of Bone and Joint Surgery and Sports Medicine Center, Guangzhou, 510630 China

Background: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus.

Objective: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.

Methods: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis.

Results: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions.

Conclusion: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.

Keywords: BMSC; Cell senescence; Osteoporosis; Syringin; Traditional Chinese Medicine

Conflicts of interest:

The authors have no manuscript-related conflict of interest to declare.

Received: February 6, 2024; Revised: August 10, 2024; Accepted: October 16, 2024; Prepublished online: October 21, 2024; Published: December 18, 2024  Show citation