A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity

Chen, Yueqi; Hu, Wenhui; Li, Xiaoming; Li, Haibo; Tang, Yong; Zhang, Lincheng; Dong, Yutong; Yang, Xiaochao; Wei, Ye; Dong, Shiwu

doi:10.1002/ctm2.240

Cited by 12 publications

(6 citation statements)

References 56 publications

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“…IL-1 can promote functional osteoclast differentiation synergistically with TNF-α ( 102 ). IL-1β also increases RANKL production in osteocytes and osteoblasts, promoting osteoclastogenesis ( 103 – 105 ). Moreover, IL-1β elevates M-CSF levels and decreases OPG levels ( 106 , 107 ).…”

Section: Mechanisms Of Bone Loss Related To Inflammasomesmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast–osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.

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Section: Mechanisms Of Bone Loss Related To Inflammasomesmentioning

confidence: 99%

Inflammasomes in Alveolar Bone Loss

Ling

Jiang

2021

Front. Immunol.

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“… 57 Also, our TRAP staining verified that overactivated osteoclasts were blamed for inflammatory bone loss. 58 , 59 For treatment, intervening in the primary diseases and inhibiting inflammation are given priority. Thus, inhibiting immune cells, cytokine, osteoclastogenesis, and osteoclast activity is applicable.…”

Section: Discussionmentioning

confidence: 99%

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Guo

Wang

Yan

et al. 2023

Cell Reports Medicine

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“…Homologous to E6AP C terminus (HECT) domain ligases transfer ubiquitin to PTEN and induce its ubiquitination [ 102 ]. Y Chen and colleagues [ 103 ] prepared a small-molecule compound named compound 17 structurally based on heclin, a HECT ligase inhibitor, and found that this compound could inhibit the ubiquitination of PTEN in osteoclasts (derived from BMDMs) stimulated by RANKL and LPS, thereby inhibiting IκBα and NF-κB p65 phosphorylation and NF-κB nuclear translocation. Decreased release of NLRP3 and IL-1β restrained osteoclast activation and bone resorption capacity, which was protective against inflammatory osteolysis.…”

Section: Pyroptosis In Macrophagementioning

confidence: 99%

Pyroptosis in Periprosthetic Osteolysis

Yin

Peng

et al. 2022

Biomolecules

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Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting in the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts may be the decisive factor. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by gasdermins (GSDMs) family, among which GSDMD is the best characterized. Recent evidence indicates that activation of NLRP3 inflammasomes and pyroptosis play a pivotal role in the pathological process of PPO. Here, we review the pathological process of PPO, the molecular mechanism of pyroptosis and the interventions to inhibit the inflammation and pyroptosis of different cells during the PPO. Conclusively, this review provides theoretical support for the search for new strategies and new targets for the treatment of PPO by inhibiting pyroptosis and inflammation.

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A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity

Cited by 12 publications

References 56 publications

Inflammasomes in Alveolar Bone Loss

Inflammasomes in Alveolar Bone Loss

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Pyroptosis in Periprosthetic Osteolysis

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