2. Academic Validation
  3. Diacerein protects against Ovariectomy-Induced bone loss via reversal of NRF2 epigenetic suppression

Diacerein protects against Ovariectomy-Induced bone loss via reversal of NRF2 epigenetic suppression

  • Biochem Pharmacol. 2026 Jan 24:247:117748. doi: 10.1016/j.bcp.2026.117748.
Liang Qiao 1,  Tao Shen 1,  Yu Ben 1,  Jian Dong 2,  Bin Liu 1,  Xiang Chen 3,  Qing Jiang 4
Affiliations

Affiliations

  • 1 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China.
  • 2 Department of Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China.
  • 3 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China. Electronic address: [email protected].
  • 4 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu, PR China. Electronic address: [email protected].
PMID: 41587594 DOI: 10.1016/j.bcp.2026.117748
Abstract

Osteoporosis (OP) is a prevalent degenerative musculoskeletal disorder in middle-aged and elderly populations, characterized by reduced bone mineral density and an increased risk of fragility fractures. Its pathogenesis is closely linked to oxidative stress imbalance; however, effective long-term therapeutic options remain limited. Here, we report that diacerein, a clinically used drug for osteoarthritis, significantly ameliorates OVX (ovariectomy)-induced bone loss and abnormal bone metabolism. Mechanistically, we demonstrate that diacerein activates the transcription and activity of NRF2 (nuclear factor erythroid 2-related factor 2), a central regulator of the antioxidant response, leading to the restoration of cytoprotective protein expression and thereby exerting protective effects against osteoporosis. The beneficial effects of diacerein on bone protection were largely abolished in Nfe2l2 knockout mice, further underscoring the essential role of NRF2. Further investigation revealed that diacerein is metabolized in vivo into rhein, which exerts potent epigenetic activity. The upregulation of NRF2 appears to be primarily mediated through rhein's inhibition of DNA methyltransferases (DNMTs) 1 and 3a. In summary, our study suggests that diacerein, a drug with a well-established safety profile and suitability for long-term use, represents a promising therapeutic candidate for the treatment of osteoporosis.

Keywords

DNA Methyltransferases; Diacerein; NRF2; Osteoporosis.

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