Fraxetin inhibits the induction of anti-Fas IgM, tumor necrosis factor-α and interleukin-1β-mediated apoptosis by Fas pathway inhibition in human osteoblastic cell line MG-63

Kuo, Po‐Lin; Huang, Yu‐Ting; Chang, Chih‐Hao; Chang, Jiunn-Kae

doi:10.1016/j.intimp.2006.02.010

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…TNF and IL-1 may increase the sensitivity of human osteoblasts to Fas induced apoptosis (32), but estradiol or raloxifene could not abrogate the effect of TNF in stimulating the expression of Fas and induction of postmenopausal human osteoblast apoptosis (10). This process could be in vitro successfully inhibited by the antioxidant molecules fraxetin and myrecitin (33, 34). Since increased TNF production is a well described consequence of estrogen deficiency (28), such small molecules may be potentially used as antiresorptive agents.…”

Section: Discussionmentioning

confidence: 99%

Fas receptor is required for estrogen deficiency-induced bone loss in mice

Kovačić

Grčević

Katavić

et al. 2010

Laboratory Investigation

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Bone mass is determined by bone cell differentiation, activity and death, which mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. We here investigate Fas as a possible mediator of bone loss induced by estrogen withdrawal. Four weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts from ovariectomized C57BL/6J (wild-type, wt) mice compared to sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas −/− mice). The number of osteoclasts increased in wt mice after OVX, while they remained unchanged in Fas −/− mice. OVX induced greater stimulation of osteoblastogenesis in Fas −/− than in wt mice, with higher expression of osteoblast specific genes. Direct effects on bone-cell differentiation and apoptosis in vivo were confirmed in vitro, where addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells. Modulation of Fas effects on bone cells may be used as a therapeutic target in the treatment of osteoresorptive disorders.

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Section: Discussionmentioning

confidence: 99%

Fas receptor is required for estrogen deficiency-induced bone loss in mice

Kovačić

Grčević

Katavić

et al. 2010

Laboratory Investigation

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“…Previous studies have reported that fraxetin is a potential anti-osteolytic agent, based on its properties to inhibit osteoblast apoptosis induced by inflammatory cytokines ( 14 ). However, osteoclasts serve an important role in osteolytic diseases, and the effects of fraxetin on these cells have not been characterized.…”

Section: Discussionmentioning

confidence: 99%

“…1A ), extracted from the Chinese herb Cortex Fraxini , has anti-inflammatory, antitumor, antioxidative, antiviral, antihyperglycemic and neuroprotective effects ( 12 , 13 ). In addition, Kuo et al ( 14 ) reported that fraxetin can inhibit interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and anti-first apoptosis signal (Fas) IgM-mediated apoptosis by suppressing the Fas signal pathway in osteoblastic MG-63 cells. These findings indicate that fraxetin might be a potential therapeutic option to prevent osteolytic diseases.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin

Wei

Zhao

et al. 2018

Int J Mol Med

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Periprosthetic osteolysis belongs to osteolytic diseases, which often occur due to an imbalance between osteoclast and osteoblast number or activity. Fraxetin, a natural plant extract, inhibits osteoblast apoptosis and has therapeutic potential for treating osteolytic diseases. However, data pertaining to the effects of fraxetin on osteoclasts are limited. In the present study, it was demonstrated that the inhibition of osteoclastogenesis by fraxetin had an important role on the therapy of titanium particle-induced osteolysis in vivo. In addition, fraxetin was demonstrated to suppress receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. Fraxetin inhibited osteoclast differentiation and function through the suppression of p38 signaling and subsequently, the suppression of osteoclast-specific gene expression, including tartrate-resistant acid phosphatase, nuclear factor of activated T-cells, cytoplasmic 1, and cathepsin K. In conclusion, fraxetin administration may have potential as a treatment method for periprosthetic osteolysis and other osteolytic diseases.

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“…Furthermore, the extracts of Emblica officinalis have been shown to induce osteoclast apoptosis and compete with NF-kB binding, resulting in decreased secretion of IL-6 (77). Additionally, fraxetin has been reported to inhibit the TNF-a and IL-1b mediated expression of Fas, upregulate the expression of FLIP, and inhibit caspase-3 and caspase-8 by inhibiting osteoblast apoptosis (78).…”

Section: Imbalanced Regulation Of Apoptosis In Osteoblasts/chondrocytes and Osteoclasts Mediates Bone Destruction In Ramentioning

confidence: 99%

Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis

et al. 2021

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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can lead to clinical manifestations of systemic diseases. Its leading features include chronic synovial inflammation and degeneration of the bones and joints. In the past decades, multiple susceptibilities for rheumatoid arthritis have been identified along with the development of a remarkable variety of drugs for its treatment; which include analgesics, glucocorticoids, nonsteroidal anti-inflammatory medications (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic response modifiers (bDMARDs). Despite the existence of many clinical treatment options, the prognosis of some patients remains poor due to complex mechanism of the disease. Programmed cell death (PCD) has been extensively studied and ascertained to be one of the essential pathological mechanisms of RA. Its dysregulation in various associated cell types contributes to the development of RA. In this review, we summarize the role of apoptosis, cell death-associated neutrophil extracellular trap formation, necroptosis, pyroptosis, and autophagy in the pathophysiology of RA to provide a theoretical reference and insightful direction to the discovery and development of novel therapeutic targets for RA.

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Fraxetin inhibits the induction of anti-Fas IgM, tumor necrosis factor-α and interleukin-1β-mediated apoptosis by Fas pathway inhibition in human osteoblastic cell line MG-63

Cited by 14 publications

References 29 publications

Fas receptor is required for estrogen deficiency-induced bone loss in mice

Fas receptor is required for estrogen deficiency-induced bone loss in mice

Inhibition of osteoclastogenesis for periprosthetic osteolysis therapy through the suppression of p38 signaling by fraxetin

Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis

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