Potential mechanisms of osteoprotegerin-induced damage to osteoclast adhesion structures via P2X7R-mediated MAPK signaling

Ma, Yonggang; Shi, Xueni; Zhao, Hongyan; Song, Ruilong; Zou, Hui; Zhu, Jiaqiao; Liu, Zongping

doi:10.3892/ijmm.2022.5115

Cited by 3 publications

(3 citation statements)

References 46 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that OVX modeling upregulates the expression of c-Fos, NFATc1, Cathepsin K, and Mmp9 in the L5 vertebrae, and these increases were partially suppressed by treating OVX mice with AC ( Figures 3A–H ). There is evidence that osteoprotegerin (OPG) acts as a negative regulator of osteoclast formation by competing for the binding between the receptor activator of NF-κB (RANK) and its ligand (RANKL) ( 28 , 29 ). Our and others’ research found that knockout of Opg resulted in severe OP phenotype with higher RANKL and osteoclast generation ( 30 , 31 ).…”

Section: Resultsmentioning

confidence: 99%

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

Xue,

Luo,

Wang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.

show abstract

Section: Resultsmentioning

confidence: 99%

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

Xue,

Luo,

Wang

et al. 2023

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Since the discovery of OPG, almost all studies on OPG have focused on its effects on osteoclast formation and bone resorption. In recent years, some researchers have explained the effect of OPG on osteoclast survival and apoptosis [ 5 , 14 , 15 ]. In addition, OPG may induce other death modes of mature osteoclasts to play its protective role.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro

Zhu

Wang

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL). The previous experiments found that OPG can induce apoptosis of mature osteoclasts in vitro, which can inhibit the activity of mature osteoclasts, thereby exerting its role in protecting bone tissue. In addition, pyroptosis is a new type of cell death that is different from apoptosis. It is unclear whether OPG can induce mature osteoclast pyroptosis and thereby play its role in protecting bone tissue. In this study, the results showed that compared with the control group, the survival rate of osteoclasts in the OPG group was significantly reduced, and the contents of IL-1β, IL-18, and LDH in the supernatant both increased. Many osteoclast plasma membranes were observed to rupture in bright fields, and OPG induced loss of their morphology. Flow cytometry was used to analyze the pyroptosis rate; OPG significantly increased the osteoclast pyroptosis rate. To further reveal the mechanism of OPG-induced osteoclast pyroptosis, we examined the expression level of pyroptosis-related genes and proteins, and the results found that OPG increased the expression of NLRP3, ASC, caspase-1, and GSDMD-N compared with the control group. In summary, OPG can induce osteoclast pyroptosis, and its mechanism is related to the expression levels of ASC, NLRP3, caspase 1 and GSDMD, which were included in the classical pathway of pyroptosis.

show abstract

“…Osteoprotegerin (OPG) is a soluble decoy receptor for RANKL made by osteoblast. OPG rule inhibits the RANK/RANKL interaction, inhibiting osteoclast overproduction even though elevated osteoclast activity culminates in bone resorption rather than bone remodelling 7 .…”

Section: Introductionmentioning

confidence: 99%

Allolobophora caliginosa coelomic fluid and extract alleviate glucocorticoid-induced osteoporosis in mice by suppressing oxidative stress and regulating osteoblastic/osteoclastic-related markers

Abdelfattah

Mohamed

Ibrahim

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Allolobophora calignosa (Ac) is a folk medicine for millennia, as it possesses many biological activities. This study aimed to investigate the chemo-preventive activity of A.calignosa coelomic fluid (AcCF) and A.calignosa extract (AcE) on glucocorticoid-induced osteoporosis (GIOP) in mice. Characterization and in vitro biological activity of AcE and AcCF has been assessed. Male CD-1 mice were subcutaneously received dexamethasone (DEX) (1 mg/kg, 5 times/week) and concurrently intraperitoneally treated with either AcCF (20 mg/kg) or AcE (45 mg/kg) every other day for 28 days. Serum and bone homogenates were subjected for qPCR and biochemical analysis. AcE and AcCF treatment significantly increased bone mineral density (BMD), bone mineral content (BMC), calcium (Ca), phosphorus (P), and calcitonin levels, whereas activity of serum alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), serum acidic phosphatase (ACP), bone acidic phosphatase (BACP) and parathyroid hormone (PTH) levels were significantly reduced compare with untreated GIOP mice. Treatment with AcE and AcCF modulates oxidative stress and downregulated Rank and Mmp9 expression, as well as increased glycosaminoglycan content in the organic bone matrix, resulting in osteoclastogenesis inhibition. Overall, AcCF and AcE show a chemo-preventive activity against GIOP by inhibiting oxidative stress and regulating expression and/or activity of osteoblast/osteoclast-related markers.

show abstract

Potential mechanisms of osteoprotegerin-induced damage to osteoclast adhesion structures via P2X7R-mediated MAPK signaling

Cited by 3 publications

References 46 publications

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

The Mechanism of Osteoprotegerin-Induced Osteoclast Pyroptosis In Vitro

Allolobophora caliginosa coelomic fluid and extract alleviate glucocorticoid-induced osteoporosis in mice by suppressing oxidative stress and regulating osteoblastic/osteoclastic-related markers

Contact Info

Product

Resources

About