PMID- 36337646
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221108
IS  - 2296-861X (Print)
IS  - 2296-861X (Electronic)
IS  - 2296-861X (Linking)
VI  - 9
DP  - 2022
TI  - S-Equol enhances osteoblastic bone formation and prevents bone loss through 
      OPG/RANKL via the PI3K/Akt pathway in streptozotocin-induced diabetic rats.
PG  - 986192
LID - 10.3389/fnut.2022.986192 [doi]
LID - 986192
AB  - BACKGROUND: This study aimed to explore whether S-Equol delays diabetes-induced 
      osteoporosis and the molecular mechanisms underlying its therapeutic effects. 
      MATERIALS AND METHODS: Thirty-five male Sprague-Dawley rats were randomized into 
      five groups. The diabetic osteoporosis (DOP) group and three S-Equol treatment 
      groups were intraperitoneally injected with streptozotocin (STZ) to develop a DOP 
      model. After the 12-week intervention, bone transformation indicators were 
      detected using an enzyme-linked immunosorbent assay kit; bone mineral density 
      (BMD) and bone microstructure were obtained using dual-energy X-ray 
      absorptiometry and microCT; morphological changes in the bone tissue were 
      investigated using HE staining; bone morphogenetic proteins were detected using 
      immunohistochemical staining. ROS17/2.8 cells were cultured in vitro, and Cell 
      Counting Kit-8 was used to test the protective effects of S-Equol in osteoblastic 
      cells in a high-fat and high-glucose environment. Furthermore, the expression of 
      osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand 
      (RANKL), estrogen receptor beta(ERbeta), phosphorylated Akt (pAKT)/protein kinase B 
      (AKT), and osteocalcin (OC) in bone tissue and ROS17/2.8 cells was assessed using 
      reverse transcription polymerase chain reaction (RT-PCR) and western blotting. To 
      determine whether ERbeta and phosphatidylinositol 3' -kinase (PI3K)/AKT signaling 
      pathways are involved in the process, LY294002 (PI3K signaling pathway inhibitor) 
      and small interfering RNA targeting ERbeta mRNA (si-ERbeta) were used to verify the 
      function of the ERbeta-mediated PI3K/AKT pathway in this process. RESULTS: After the 
      12-week intervention, S-Equol enhanced BMD, improved bone microarchitecture in 
      DOP rats (P < 0.05), and improved markers of bone metabolism (P < 0.05). In 
      vitro, 10(-6) mmol/L S-Equol was selected to significantly protect osteoblasts 
      from high- and high-glucose environments (P < 0.05). Gene expression of OPG, ERbeta, 
      pAKT/AKT, and OC was upregulated compared to the DOP group, and RANKL was 
      downregulated compared to the DOP group (P < 0.05) both in bone tissue and 
      osteoblastic cells. The promotion of OPG and pAKT/AKT is mediated by LY294002 and 
      siERbeta. CONCLUSION: S-Equol binds to ERbeta to regulate OPG/RANKL via the PI3K/AKT 
      pathway and improve DOP. Our results demonstrate the potential role of S-Equol in 
      the treatment of DOP by targeting ERbeta. Thus, S-Equol may have the potential to be 
      an adjuvant drug for treating DOP.
CI  - Copyright (c) 2022 Xu, Xu, Li, Cui, Zhang, Ni and Wang.
FAU - Xu, Zhe
AU  - Xu Z
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Xu, Jing
AU  - Xu J
AD  - Department of Endocrinology, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Li, Shuo
AU  - Li S
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Cui, Hanqiang
AU  - Cui H
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Zhang, Guiming
AU  - Zhang G
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Ni, Xiangmin
AU  - Ni X
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Nutrition, Xinqiao Hospital, Army Medical University (Third 
      Military Medical University), Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20221021
PL  - Switzerland
TA  - Front Nutr
JT  - Frontiers in nutrition
JID - 101642264
PMC - PMC9633996
OTO - NOTNLM
OT  - AKT
OT  - S-Equol
OT  - diabetic osteoporosis (DOP)
OT  - estrogen receptor beta (ERbeta)
OT  - osteoprotegerin (OPG)
OT  - receptor activator of nuclear factor kappa-B ligand (RANKL)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/08 06:00
MHDA- 2022/11/08 06:01
PMCR- 2022/01/01
CRDT- 2022/11/07 04:14
PHST- 2022/07/04 00:00 [received]
PHST- 2022/10/07 00:00 [accepted]
PHST- 2022/11/07 04:14 [entrez]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2022/11/08 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnut.2022.986192 [doi]
PST - epublish
SO  - Front Nutr. 2022 Oct 21;9:986192. doi: 10.3389/fnut.2022.986192. eCollection 
      2022.