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. 2026 Feb 17.
doi: 10.1002/ptr.70200. Online ahead of print.

Leonurine Maintains BMSCs Stemness From Osteoporotic Rats Through Inhibiting Ferroptosis Depending on the JNK Signaling Pathway

Dongmei Lan  1   2   3 , Haijiang Liu  2   4 , Chao Yao  1   2   3 , Xue Li  1   2   3 , Yurong Chen  1   2   3 , Dan Wang  5 , Yan Wang  2   3   6 , Jue Wang  1   2   3 , Yizhun Zhu  7 , Shengcai Qi  1   2   3
Affiliations

Leonurine Maintains BMSCs Stemness From Osteoporotic Rats Through Inhibiting Ferroptosis Depending on the JNK Signaling Pathway

Dongmei Lan et al. Phytother Res. .

Abstract

Osteoporosis (OP) is a chronic bone metabolic disease in which the balance between osteoblasts and osteoclasts is broken. Leonurine can protect BMSCs from oxidative stress, while the role and molecular mechanism of leonurine on OP is unclear. The primary BMSCs from OP rats (OP-BMSCs) were extracted and cultured in vitro. Next, we observed the effects of different concentrations of leonurine on cell viability, ROS level and osteoblast differentiation. Additionally, the change levels of ferroptosis and bone microstructure were examined. RNA sequencing was used to analyze the signaling pathway and the MAPK signaling pathway was explored in vitro. Finally, the functions of osteoclasts were estimated. Leonurine downregulated ROS levels, upregulated the expression of antioxidative genes and osteogenic-related markers in OP-BMSCs via inhibiting ferroptosis depending on upregulating the phosphorylation of JNK. Additionally, the supernatant of OP-BMSCs promoted the M1 polarization and inhibited M2 polarization, which will be suppressed after co-culture of leonurine and OP-BMSCs in vitro. Leonurine could promote the osteogenic function of BMSCs via the inhibition of ferroptosis depending on the JNK signaling pathway and inhibit osteoclastic differentiation by the promotion of M2 polarization, which represents a potential therapeutic approach for OP.

Keywords: BMSCs; JNK signaling pathway; Leonurine; ferroptosis; osteoblastic differentiation; osteoclastic differentiation.

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