Isoimperatorin attenuates bone loss by inhibiting the binding of RANKL to RANK

Li, HaiShan; Deng, Wei; Qin, Qiuli; Lin, Yuewei; Li, Teng; Mo, Guo‐ye; Shao, Yang; Tang, Yi; Yuan, Kai; Xu, Liangliang; Li, YongXian; Zhang, Shuncong

doi:10.1016/j.bcp.2023.115502

Cited by 7 publications

(2 citation statements)

References 55 publications

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“…Postmenopausal estrogen de ciency is the main mechanism of PMOP [31] .Estrogen de ciency can increase the levels of immune factors, which can interfere with bone metabolism through mechanisms such as the OPG/RANKL pathway. This can lead to bone metabolism imbalance, bone loss, and eventually the development of postmenopausal osteoporosis [8,32,33] . The data of this study also proved this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Study on the trend of changes in the gut microbiota of rats with ovariectomy-induced postmenopausal osteoporosis and the effect of estrogen intervention

lei,

Cheng,

Xia

et al. 2023

Preprint

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Postmenopausal osteoporosis (PMOP) is a common primary osteoporosis. With the aging of the population, it is becoming a major disease that endangers health and quality of life. The purpose of this study was to explore the effect of gut microbiota on PMOP by observing the changes in the levels of estradiol, bone density, and gut microbiota diversity in rats after 3 months of OVX surgery. We randomly divided 60 female SD rats into four groups: baseline group (6 rats), sham-operated group (18 rats), model group (18 rats), and estrogen-treated group (18 rats). The ovariectomy model of postmenopausal osteoporosis was established by performing bilateral ovariectomy. After surgery, 6 rats from each group were randomly sacrificed every 30 days and assessed. After 90 days, all rats were sacrificed and their body weight, bone mineral density (BMD), tissue mineral density (TMD), trabecular bone parameters, femoral bone morphology, hormone levels, and gut microbiota diversity were assessed. We found that OVX led to a decrease in BMD, TMD, and serum estradiol levels in rats, and Increases TNF-α levels. The bone micro-architecture and tissue morphology were also changed, with trabecular fractures, thinning, and decreased numbers. The gut microbiota diversity also changed. Estrogen treatment could improve these changes. OVX leads to a sustained decrease in estrogen levels in rats, which results in progressive bone loss. This is associated with an imbalance in the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Study on the trend of changes in the gut microbiota of rats with ovariectomy-induced postmenopausal osteoporosis and the effect of estrogen intervention

lei,

Cheng,

Xia

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…De Matos et al conducted a study showing that Isoimperatorin (ISO), a bioactive furanocoumarin found in traditional Chinese herbal medicines, inhibited the combination of RANKL and RANK, resulting in decreased NFATc1 expression and suppressed osteoclast formation (Li et al 2023 ). In another study by Fan et al, it was observed that ISO reduced the secretion of pro-inflammatory factors and inhibited the differentiation of human periodontal membrane fibroblasts (hPDLCs) into osteoclasts under RANKL stimulation (Fan et al 2023 ).…”

Section: The Rankl/rank Signaling Pathway Activates Nfatc1mentioning

confidence: 99%

Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

Zheng,

Liu,

Deng

et al. 2024

Mol Med

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

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