The effect and molecular mechanism on regulation of bone remodeling by two Chinese herbal formulas, Er-Zhi-Wan and Du-Zhong-Wan

Title : The effect and molecular mechanism on regulation of bone remodeling by two Chinese herbal formulas, Er-Zhi-Wan and Du-Zhong-Wan

Abstract:

Bone homeostasis is maintained by bone remodeling process that includes osteoblast-mediated bone formation and osteoclast-mediated bone resorption. The excess of osteoclastic bone resorption over osteoblastic bone formation results in bone-related diseases such as osteoporosis. However, the mechanism of osteoporosis and therapeutical drugs is still under investigated. We focus on two kidney-nourishing Chinese herbal formulas, one is Er-Zhi-Wan which is composed of Eclipta prostrata (L.) L. and Ligustrum lucidum Ait., and the other is Du-Zhong-Wan which is composed of Eucommiae cortex and Dipsaci Radix. In ovariectomized mice, administration of extract of Er-Zhi-Wan prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. In bone marrow mesenchymal stem cells (BMSC), the m6A MeRIP-Seq analysis indicated that Er-Zhi-Wan extract treatment altered mRNA m6A modification of genes associated with osteoblastogenesis and upregulated the expression of methyltransferase METTL3 and METTL14, indicating that METTL3-mediated m6A methylation is involved. For the Du-Zhong-Wan, DZW treatment significantly enhanced the healing process of osteoporotic fractures. Single-cell sequencing revealed that Du-Zhong-Wan significantly increased the proportion of Lepr+ BMSCs and Podxl+ ECs subclusters, increased the expression of VEGF and slit3, the crucial mediators of the interaction between BMSCs and endothelial cells. The data indicates that Er-Zhi-Wan and Du-Zhong-Wan exert distinct mechanism for regulating bone modeling, suggesting potential novel treatment for osteoporosis.

Audience Take Away Notes: 

• The multi-target effect of two Chinese herbal formulas, Er-Zhi-Wan and Du-Zhong-Wan on regulating bone remodeling. It is beneficial for treating osteoporosis.
• The novel targets, such as METTL3 and Piezo1, were found.
• According Traditional Chinese medicine theory, the distinct action of tonifying Kidney-Yang and Kidney-Yin was elucidated.
• The multi-omics methods, such as m6A methylation sequencing, and single-cell sequencing were used for elucidating the mechanism

Biography:

Liu studied pharmacology at the Shenyang pharmaceutical University, Shenyang, China and graduated as Dr. in 2006. She then joined the research group at Dalian Institute of Chemical Physics, Chinese academy of Sciences (2006-2013) and Dalian medical University (2013-2020). In 2018, She researched as a visiting scholar at University of Colorado Anschutz Medical Campus. In 2020, she obtained the position of a Professor at Shandong University of Traditional Chinese Medicine. She has published more than 40 research articles in SCI(E) journals.