Page 239 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-56

Enterodiol and enterolactone regulate ERRɑ-mediated mitochondrial

biogenesis in osteoclastogenesis

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2
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Ming-Lung Hsu, Chun-Han Hou, Po-Chun Chen*

1 School of Life Science, National Taiwan Normal University, Taipei city, Taiwan
2 Department of Orthopedic Surgery National Taiwan University Hospital, Taipei city, Taiwan
* E-mail: pcchen@ntnu.edu.tw

Abstract
Osteoporosis (OP) is the most common bone disease in the elderly and postmenopausal
women, caused by excessive bone resorption over bone formation. Bone remodeling relies on
osteoclasts, osteoblasts, and osteocytes, with osteoclasts being the only cells that degrade bone
matrix. Osteoclast formation requires high energy and is regulated by mitochondrial biogenesis
factors such as PGC-1β and ERRα. Targeting osteoclast metabolism may offer new therapeutic
approaches for OP and other bone-loss diseases. Enterodiol (END) and enterolactone (ENL)
are plant-based polyphenolic compounds. Both END and ENL have been reported have
antioxidant and estrogen-like physiological regulatory functions. However, previous studies
have not clearly elucidated the mechanisms of END and ENL in regulating osteoclast
differentiation and function, which require further investigation. In this study, we investigate
the effect of END and ENL on osteoclast differentiation. Our preliminary data showed 100 μM
END and ENL significantly inhibit osteoclast differentiation and bone resorption. Treatment
with 100 μM END and ENL reduced the expression levels of osteoclast differentiation markers.
Transcriptome analysis suggests that END and ENL affect oxidative phosphorylation during
osteoclastogenesis. Treatment with END and ENL also decreased mitochondrial DNA (mtDNA)
copy number, components of mitochondrial respiratory, oxygen consumption rate (OCR) and
mitochondrial biogenesis markers. Molecular docking results showed that END and ENL might
interact with ERRɑ on the receptor level. Taken together, our findings demonstrated that END
and ENL may influence osteoclast differentiation and function by regulating PGC-1β/ERRɑ-
dependent mitochondrial energy metabolism, offer new therapeutic reagents for preventing OP.

Keywords: Enterodiol; Enterolactone; ERRɑ; Mitochondrial biogenesis; Osteoclast
differentiation