scholarly journals NIK inhibitor impairs chronic periodontitis via suppressing non-canonical NF-κB and osteoclastogenesis

2020 ◽  
Vol 78 (7) ◽  
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Lei Wang
Keyword(s):  
Alveolar Bone ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Mice Model ◽  
Western Blot Assay ◽  
Beneficial Effects ◽  
Genes Expression ◽  
Receptor Activator

ABSTRACT Periodontitis is an inflammatory disease that causes damages to periodontium and alveolar bone. Overactivation and formation of osteoclasts can cause bone destruction, which contributes to periodontitis development. Receptor activator of nuclear factor κB ligand (RANKL)-mediated NF-κB signaling plays an essential role in osteoclasts differentiation. We aimed to study the effects of NIK-SMI1, an NF-κB-inducing kinase (NIK) inhibitor, on the osteoclastogenesis in vitro and periodontitis progression in vivo. A ligature-induced mice model of periodontitis was incorporated to test the potential therapeutic effect of NIK-SMI1 on periodontitis. The target protein and mRNA expression levels were determined by Western blot assay and real-time PCR assay, respectively. We found that the administration of NIK-SMI1 strongly inhibited the RANKL-stimulated non-canonical NF-κB signaling as demonstrated by decreased nuclear p52 expression and activity. Blocking NIK activity also resulted in reduced osteoclasts specific genes expression and enhanced IFN-β expression. NIK-SMI1 treatment resulted in attenuated periodontitis progression and pro-inflammatory cytokines expression in vivo. Our study suggested that NIK-SMI1 exerts beneficial effects on the mitigation of osteoclastogenesis in vitro and periodontitis progression in vivo. Application of NIK-SMI1 may serve as a potential therapeutic approach for periodontitis.

scholarly journals Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

2020 ◽  
Vol 34 ◽  
pp. 205873842097489
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Yingjie Wang
Keyword(s):  
Alveolar Bone ◽  
Immune Cell ◽  
Critical Role ◽  
Therapeutic Drug ◽  
Mice Model ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

scholarly journals Osteoclasts are important for bone angiogenesis

Blood ◽  
2010 ◽  
Vol 115 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Frank C. Cackowski ◽  
Judith L. Anderson ◽  
Kenneth D. Patrene ◽  
Rushir J. Choksi ◽  
Steven D. Shapiro ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Angiogenic Factor ◽  
Adult Mice ◽  
Parathyroid Hormone Related Protein ◽  
Receptor Activator ◽  
Metalloproteinase 9

Abstract Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-κB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9−/− mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.

scholarly journals Inflamm-Aging-Related Cytokines of IL-17 and IFN-γ Accelerate Osteoclastogenesis and Periodontal Destruction

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jingyi Tan ◽  
Anna Dai ◽  
Lai Pan ◽  
Lan Zhang ◽  
Zhongxiu Wang ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Tissue Loss ◽  
Interleukin 17 ◽  
Age Related ◽  
Periodontal Destruction ◽  
Ifn Γ

Periodontal disease (PD), as an age-related disease, prevalent in middle-aged and elderly population, is characterized as inflammatory periodontal tissue loss, including gingival inflammation and alveolar bone resorption. However, the definite mechanism of aging-related inflammation in PD pathology needs further investigation. Our study is aimed at exploring the effect of inflamm-aging-related cytokines of interleukin-17 (IL-17) and interferon-γ (IFN-γ) on osteoclastogenesis in vitro and periodontal destruction in vivo. For receptor activator of nuclear factor-κB ligand- (RANKL-) primed bone marrow macrophages (BMMs), IL-17 and IFN-γ enhanced osteoclastogenesis, with the expression of osteoclastogenic mRNA (TRAP, c-Fos, MMP-9, Ctsk, and NFATc1) and protein (c-Fos and MMP-9) upregulated. Ligament-induced rat models were established to investigate the role of IL-17 and IFN-γ on experimental periodontitis. Both IL-17 and IFN-γ could enhance the local inflammation in gingival tissues. Although there might be an antagonistic interaction between IL-17 and IFN-γ, IL-17 and IFN-γ could facilitate alveolar bone loss and osteoclast differentiation.

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