Senile osteoporosis is a form of primary osteoporosis with complex underlying mechanisms and is a major pathological contributor to age-related bone loss. At present, no pharmacological agents have been developed specifically for senile osteoporosis. With the rapid ageing of the global population, senile osteoporosis has become a serious public health challenge.

Recently, a research team led by Prof. CHEN Chang at the Institute of Biophysics of the Chinese Academy of Sciences systematically investigated the protective effects and molecular mechanism of naringenin (NAR) against age-related bone loss.

Using a natural ageing mouse model, the researchers demonstrated that NAR counteracts bone loss by stimulating bone formation and restraining bone resorption, while identifying Runx2, a key transcription factor in osteogenic differentiation, as a direct molecular target of NAR.

The study was published in the British Journal of Pharmacology on August 16, 2026.

NAR is a plant-derived flavonoid commonly found in the diet and is known for its anti-inflammatory, antioxidant, and metabolic regulatory activities. Although previous studies have suggested that NAR may benefit bone health, its direct molecular target and effects in age-related osteoporosis have remained unclear.

Using a physiologically relevant natural ageing mouse model, the researchers found that NAR treatment significantly raised bone mineral density, preserved trabecular microarchitecture, and strengthened skeleton. Histomorphometric analyses further showed that NAR accelerated the mineral apposition rate and bone formation while reducing osteoclast activity and bone resorption. Consistently, NAR stimulated osteogenic differentiation and mineral deposition in cultured cells. These findings demonstrate that NAR exerts a dual action on bone remodelling by simultaneously enhancing bone formation and limiting bone resorption.

To elucidate the underlying mechanism, the researchers combined RNA interference, NAR-biotin affinity pull-down and mass spectrometry with molecular docking and molecular dynamics simulations, surface plasmon resonance, drug affinity responsive target stability, and cellular thermal shift assays. The results showed that NAR interacts directly with Runx2 and promotes its osteogenic function.

The findings reveal a previously unrecognized mechanism underlying the skeletal effects of NAR and highlight this dietary flavonoid as a promising natural-product candidate for the prevention and treatment of senile osteoporosis.

Figure 1. Schematic illustration of how naringenin alleviates senile osteoporosis by targeting Runx2

(Image by CHEN Chang's group)

Article link: https://doi.org/10.1111/bph.70631

Contact: CHEN Chang

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

E-mail: changchen@ibp.ac.cn

(Reported by Prof. CHEN Chang's group)