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PP-72

Multi-component osteogenic potential of Clematis montana in counteracting

glucocorticoid-induced calcification loss in zebrafish

3
4
1
Wen-Ying Lin, Cheng-Huan Peng, Yi-Tzu Lin, Chia-Ying Li, Szu-Chieh Wang,
2
5
Ming-Der Lin* ,1,5,6

1 Institute of Medical Science, Tzu Chi University, Hualien, 97004, Taiwan
2 Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical
Foundation, Hualien, 97002, Taiwan
3 School of Pharmacy, Tzu Chi University, Hualien, 97004, Taiwan
4 Department of Applied Chemistry, National Pingtung University, Pingtung, 90003, Taiwan
5 Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien,
97004, Taiwan
6 Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital,
Buddhist Tzu Chi Medical Foundation, Hualien, 97002, Taiwan
* Email: mingder@gms.tcu.edu.tw

Abstract
Osteoporosis is a chronic metabolic bone disorder characterized by reduced bone mass,
microstructural deterioration, and elevated fracture risk. Clinically available bone-anabolic
drugs are constrained by high costs and safety concerns, underscoring the need for safer,
affordable alternatives. Clematis montana Buch.-Ham. (Chuan-Mu-Tong, CMT), a traditional
Chinese herb, has long been used to alleviate inflammation and treat conditions associated with
kidney essence deficiency, a concept historically linked to osteoporosis. This study
demonstrated that CMT water extract reverses Dex-induced vertebral calcification deficiency
and enhances osteoblast formation in zebrafish models of osteoporosis in a dose-dependent
manner. Notably, beyond counteracting Dex-induced bone loss, CMT also promoted bone
formation in both larval vertebrae and adult scale models, indicating its intrinsic osteogenic
activity. Gene set enrichment analysis revealed that CMT mitigates Dex-induced calcification
loss primarily by promoting osteoblast differentiation, a finding further validated in transgenic
zebrafish expressing EGFP-labeled osteoblasts. Among the bioactive components,
syringaresinol—a lignan identified in CMT—was experimentally confirmed to contribute to
this effect. LC-MS/MS profiling additionally identified five bioactive compounds with reported
osteogenic potential. Network pharmacology suggested that these compounds act
synergistically to stimulate osteoblast differentiation through targets such as NFKB1 and
HIF1A. Consistently, transcriptomic analysis showed that CMT reverses Dex-mediated
suppression of ossification genes via both TNF-α and HIF-1 signaling pathways. Together,
these findings underscore the multi-component, multi-target actions of CMT, offering
mechanistic insights into its bone-anabolic effects and supporting its potential as a therapeutic
option for osteoporosis.

Keywords: Clematis montana; Chuan-Mu-Tong; Zebrafish; Osteoporosis; Osteoblastogenesis