Wedelolactone inhibits osteoclastogenesis but enhances osteoblastogenesis through altering different semaphorins production

Deng, Xinyi; Liang, Lina; Zhu, Duzhang; Zheng, Liqin; Yu, Jinghua; Meng, Xiang-Ling; Zhao, Yining; Sun, Xiao Xin; Pan, Taowen; Li, Yanqiu

doi:10.1016/j.intimp.2018.04.037

Cited by 27 publications

(18 citation statements)

References 26 publications

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“…In our in vitro study, Sema4D could reduce the expression of OCN and ALP in Plexin-B1 positive osteoblast, which was similar to previous report [45] . However, in vivo study of UAC-induced early-stage OA, the expression of Runx2, OSX, OCN and ALP was increased.…”

Section: Discussionsupporting

confidence: 92%

Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

Zhang¹,

Lü²,

T³

et al. 2021

Preprint

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Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

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Section: Discussionsupporting

confidence: 92%

Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

Zhang¹,

Lü²,

T³

et al. 2021

Preprint

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“…[209], breast [210], and pituitary adenomas [211]. It has been reported to exert immunomodulatory, antiinflammatory [212,213], antimyotoxic, antihemorrhagic [214], and antioxidant activities [215], inhibit osteoclastogenesis, and enhance osteoblastogenesis [216,217]. Wedelolactone can suppress LPS-induced inflammation in mouse embryo fibroblasts via suppression of NF-κB activity [218].…”

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

157

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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“…At the same time, wedelolactone enhanced osteoblastogenesis through promoting the production of Sema7A and Sema7A-PlexinC1-Beta1 complex formation in BMSCs. These results suggested that wedelolactone enhanced osteoblastogenesis but inhibited osteoclastogenesis through altering semaphorin family proteins [50].…”

Section: Chinese Herbal Drugs That Enhance Osteoblastogenesis And/or mentioning

confidence: 82%

Traditional Chinese Medicine Therapy for Targeting Osteoblastogenesis

Li¹

2019

Osteogenesis and Bone Regeneration

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Osteoblasts are derived from bone marrow mesenchymal stem cell (BMSC) precursors, which differentiate into mature osteoblasts and mediate bone formation. This process is called osteoblastogenesis. A deficiency in osteoblastogenesis of BMSCs can result in bone-related diseases including osteoporosis. Thus, developing drugs for targeting osteoblastogenesis from BMSCs has become one of the therapeutic strategies for osteoporosis. In China, kidney-nourishing Chinese herbal drugs such as ER-Zhi-Wan have been believed to be potential for treating osteoporosis through targeting osteoblast proliferation and differentiation. The key pathways for regulating osteoblastogenesis include canonical and noncanonical Wnt pathway, semaphorin-mediated pathway, and MAPK-mediated BMP2-Smad pathway. Some natural products have been confirmed to regulate more than one pathway and exert multi-target effect through the use of one compound or combined use of more than two compounds, such as wedelolactone and oleonuezhenide. In addition, tissue engineering provides a promising strategy in the field for targeting osteoblastogenesis. New types of biomaterials including hydroxyapatite (HAp) combined with Chinese medicine can exert enhanced effect on osteoblastogenesis and provide new therapy for treating osteoporosis.

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Wedelolactone inhibits osteoclastogenesis but enhances osteoblastogenesis through altering different semaphorins production

Cited by 27 publications

References 26 publications

Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Traditional Chinese Medicine Therapy for Targeting Osteoblastogenesis

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