Osteoporosis remains a major global health challenge, particularly in postmenopausal women. Current therapies are limited by cost, side effects and incomplete efficacy. As a result, there is growing interest in safe, repurposable molecules such as melatonin, a hormone known for regulating circadian rhythms and shown in emerging studies to influence bone metabolism.

Guo et al. investigated the mechanisms underlying melatonin’s effects on bone formation using both MC3T3-E1 osteoblast precursor cells and an ovariectomised mouse model of osteoporosis. They combined functional assays, gene manipulation and in vivo analyses to explore the role of cathepsin D (CTSD).
The authors report that melatonin enhances osteoblast differentiation and mineralisation, increases bone strength and suppresses osteoclast activity. Mechanistically, these effects are mediated through upregulation of CTSD and modulation of key signalling pathways, including RANKL/OPG and Wnt/ β-catenin. CTSD knockdown abolishes these benefits, supporting a causal role.

Overall, this study provides important mechanistic insight, and highlights melatonin as a promising, accessible candidate for osteoporosis therapy, making it of interest to researchers in bone biology and translational medicine.

Read the full article in Journal of Molecular Endocrinology https://doi.org/10.1530/JME-25-0220