Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways

Yang, Zhengmeng; Lu, Feng; Wang, Ming; Li, Yucong; Bai, Shanshan; Lu, Xuan; Wang, Haixing; Zhang, Xiaoting; Wang, Yaofeng; Lin, Sien; Tortorella, Micky D.; Li, Gang

doi:10.3390/nu14102106

Cited by 12 publications

(6 citation statements)

References 47 publications

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“…Lignans also alleviate neuroinflammation, reducing brain damage by preserving BDNF expression and modulating neurotransmitter levels. Surprisingly, some of the lignans showed impressive efficacy on postmenopausal symptoms compared to extrinsic hormones such as parathyroid hormone or estrogen [ 88 , 103 ]. It was confirmed that TNF-α expression was more strongly suppressed when treated with lignans derived from Sambucus Willaimsii compared to parathyroid hormone treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Zhengmeng Yang et al also discovered the anti-osteoclastogenesis effect of Ses to be mediated by NF-κB pathway inhibition, which reduces the expression of CTSK and tartaric-acid phosphatase (TRAP) in osteoclasts [ 102 ]. Moreover, healing of osteoporotic fractures in C57BL/6 mice following OVX surgery was improved by oral administration of Ses [ 103 ]. Ses upregulated the expression of VEGF, an angiogenesis marker, along with bone morphogenetic protein 2 (BMP2) and SOX9, both chondrogenesis markers.…”

Section: Anti-menopausal Effects Of Lignansmentioning

confidence: 99%

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Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

Jang

Kim

Cho

2022

IJMS

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Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

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Section: Discussionmentioning

confidence: 99%

Section: Anti-menopausal Effects Of Lignansmentioning

confidence: 99%

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

Jang

Kim

Cho

2022

IJMS

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“…Quercetin is identified as an antiosteoporotic flavonoid, which promotes osteogenesis, antioxidant expression, angiogenesis, osteoclast, and adipocyte apoptosis, while inhibiting RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress, and inflammatory response [35]. Sesamin, a member of the lignan family, has estrogenic activity and plays an important role in healing osteoporotic fracture by activating angiogenesis and chondrogenesis [36]. Moreover, existing study reveals that sesamin could promote osteogenesis by upregulating the Wnt/ β-catenin pathway and inhibit osteoclastogenesis by downregulating the NF-κB pathway, suggesting that it could be a therapeutic medication for osteoporosis treatment [37].…”

Section: Discussionmentioning

confidence: 99%

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Zhang

Chen

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Glucocorticoid-induced osteoporosis (GIOP) is a musculoskeletal disease with increased fracture risk caused by long-term application of glucocorticoid, but there exist few effective interventions. Zuogui Pill (ZGP) has achieved clinical improvement for GIOP as an ancient classical formula, but its molecular mechanisms remain unclear due to scanty relevant studies. This study aimed to excavate the effective compounds and underlying mechanism of ZGP in treating GIOP and construct relative ceRNA network by using integrated analysis of bioinformatics analysis and experimental validation. Results show that ZNF702P is significantly upregulated in GIOP than normal cases based on gene chip sequencing analysis. Totally, 102 ingredients and 535 targets of ZGP as well as 480 GIOP-related targets were selected, including 122 common targets and 8 intersection targets with the predicted mRNAs. The ceRNA network contains one lncRNA (ZNF702P), 6 miRNAs, and 8 mRNAs. Four hub targets including JUN, CCND1, MAPK1, and MAPK14 were identified in the PPI network. Six ceRNA interaction axes including ZNF702P-hsa-miR-429-JUN, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-CCND1, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-MAPK1, and ZNF702P-hsa-miR-24-3p-MAPK14 were obtained. By means of molecular docking, we found that all the hub targets could be effectively combined with related ingredients. GO enrichment analysis showed 649 biological processes, involving response to estrogen, response to steroid hormone, inflammatory response, macrophage activation, and osteoclast differentiation, and KEGG analysis revealed 102 entries with 36 relative signaling pathways, which mainly contained IL-17 signaling pathway, T cell receptor signaling pathway, FoxO signaling pathway, the PD-L1 expression and PD-1 checkpoint pathway, MAPK signaling pathway, TNF signaling pathway, Estrogen signaling pathway, and Wnt signaling pathway. Our experiments confirmed that ZNF702P exhibited gradually increasing expression levels during osteoclast differentiation of human peripheral blood monocytes (HPBMs) induced by RANKL, while ZGP could inhibit osteoclast differentiation of HPBMs induced by RANKL in a concentration-dependent manner. Therefore, by regulating inflammatory response, osteoclast differentiation, and hormone metabolism, ZGP may treat GIOP by regulating hub target genes, such as JUN, CCND1, MAPK1, and MAPK14, and acting on numerous key pathways, which involve the ZNF702P-based ceRNA network.

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“…The peroxidase-streptavidin substrate kit (DAKO, Carpinteria, CA, USA) was applied for substrate reaction. Additionally, the images were taken by a semi-automatic digitizing image analysis system (OsteoMetrics, Atlanta, GA, USA) [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis

Yang

Hou

et al. 2023

IJMS

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Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/β-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.

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Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways

Cited by 12 publications

References 47 publications

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis

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