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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.

Sec. Biomechanics

Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1639117

Ipriflavone ameliorates intervertebral disc degeneration by inhibiting osteoporosis of vertebral body and pyroptosis of the nucleus pulposus in instability of lumbar spine and diabetic mice

Provisionally accepted
Qi  SunQi Sun1*Hai-Jing  ZhangHai-Jing Zhang1Hui  WangHui Wang1Ji  GangJi Gang1Yaheng  ZhaoYaheng Zhao1Gao-Cen  LiGao-Cen Li1Shao- Shi  GuoShao- Shi Guo1Lu-Feng  LinLu-Feng Lin1Yujie  JinYujie Jin1Xue-Li  ZhangXue-Li Zhang1Xin-Yu  NanXin-Yu Nan2*Chang-Cheng  LiuChang-Cheng Liu1*Guo-Bin  LiuGuo-Bin Liu1*
  • 1The First hospital of Hebei Medical University, Shijiazhuang, China
  • 2Hebei Medical University, Shijiazhuang, China

The final, formatted version of the article will be published soon.

Background: Diabetes mellitus (DM) is a chronic metabolic disease, which can not only induce osteoporosis but also accelerate intervertebral disc degeneration(IVDD).Ipriflavone(IP), as a derivative of isoflavones, can not only control the level of blood glucose, but also improve the regulation of osteoporosis and cartilage extracellular matrix metabolism. However, there is no study on whether IP can effectively improve DM with IVDD.: Sixty healthy female C57BL/6J mice were randomly assigned into five groups (Sham, Instability of lumbar spine (ILS), streptozotocin (STZ), ILS+STZ and ILS+STZ +IP groups; 12 per group). The body weight, fasting glucose and blood insulin levels were evaluated in each group of mice. The pathology of DM with IVDD was assessed by Micro-CT(μCT), Van Gieson (VG) staining, Alcian blue (Ab)staining, immunohistochemistry, western blot and real-time polymerase chain reaction (RT-PCR). Results: IP significantly lowed fasting blood glucose and blood insulin levels. Histomorphological analysis revealed that IVDD was significantly exacerbated by the coexistence of ILS and DM, and markedly alleviated by IP. In details, IP markedly improved osteoporosis and microarchitecture of EP and vertebrae. Furthermore, IP ameliorated the cartilage extracellular matrix degradation, significantly increased Aggrecan and Col II expression and decreased the expression of MMP13 and ADAMTS-4. Moreover, IP inhibited EP sclerosis and NP pyroptosis by decreasing Runx2, Osterix, NLRP3, ASC, N-GSDMD and caspase1 expression.The coexistence of ILS and DM further aggravates abnormal metabolic pathology and IVDD, which could be retarded by IP, suggesting that IP may be a potential therapeutic target for amelioration of the progression of DM with IVDD.

Keywords: diabetes, pyroptosis, Osteoporosis, Intervertebral Disc Degeneration, Ipriflavone

Received: 01 Jun 2025; Accepted: 21 Jul 2025.

Copyright: © 2025 Sun, Zhang, Wang, Gang, Zhao, Li, Guo, Lin, Jin, Zhang, Nan, Liu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Qi Sun, The First hospital of Hebei Medical University, Shijiazhuang, China
Xin-Yu Nan, Hebei Medical University, Shijiazhuang, China
Chang-Cheng Liu, The First hospital of Hebei Medical University, Shijiazhuang, China
Guo-Bin Liu, The First hospital of Hebei Medical University, Shijiazhuang, China

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