Artesunate reverses BMSC senescence and ameliorates osteoporosis by upregulating NSD2
Hui Jin1, Yangyang Zhang1, Chunying Hou1
1Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Background:
Senile osteoporosis (SOP) is a typical ageing-related bone disease that is primarily prevalent in elderly people. The present study aimed to examine the therapeutic efficacy of artesunate (ART) administration in SOP and aged bone marrow stromal cells (BMSCs) and investigate its underlying mechanisms.
Methods:
18-month-old C57BL/6J mice were used as an aged mouse model and treated with ART through intragastric administration. Micro-CT analysis was used to evaluate the effects of ART on age-related bone loss in vivo. The protective effects of ART on age-related and H2O2-induced aged BMSCs were separately assessed in vitro. Further experiments were performed to investigate the mechanism by which ART prevents BMSC senescence.
Results:
Intragastric administration of ART effectively alleviated age-related bone loss and BMSC senescence in SOP mice. ART treatment rescued the aged phenotypes and ameliorated the ROS accumulation of H2O2-induced aged BMSCs in vitro. Furthermore, the histone methyltransferase NSD2 might be an important mediator of the ability of ART to delay BMSC senescence.
Conclusions:
This study demonstrated that ART might relieve BMSC senescence and SOP by regulating the expression of NSD2. We identified a crucial anti-osteoporotic function of ART in SOP, providing new insight into the treatment of age-related bone loss.

