International Journal of Oral Science
·
2024
·Vol. 16
·期 1
·1-11
·
IF 10.8
Wang Wen,Wang Qian,Sun Shiying,Zhang Pengfei,Li Yuyu,Lin Weimin,Li Qiwen,Zhang Xiao,Ma Zhe,Lu Haiyan
Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.
研究领域:
牙科学
·
正畸学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 15
·期 5
·3048-3054
·
IF 1.692
Wenting Zhao,Zhen Wang,Zewei Sun,Shuai Wang,Mingjie Wu,Liangrong Zheng
Elevated blood glucose levels contribute to a series of complications in patients with diabetes mellitus, including chronic ulcers and accelerated atherosclerosis. Dysregulated endothelial migration induced by high glucose is important in vascular‑associated complications. In the present study, cluster of differentiation (CD)97/adhesion G protein‑coupled receptor 5 (ADGRE5), a member of the G protein‑coupled receptor protein family, stimulated angiogenesis was investigated to determine its role in cell models of diabetes mellitus using lentivirus‑mediated overexpression and siRNA transfection. The results revealed reduced expression in high glucose‑treated human umbilical vein endothelial cells and in the endothelium of diabetic mice. Among the three CD97 isoforms, the majority of the expression of CD97 (EGF1,2,5) in the endothelial cells was regulated by high levels of glucose. Using stable lentivirus‑mediated transfection and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (Cas9) technology, the present study constructed CD97‑overexpression and CD97‑knockout endothelial cell lines. Migration assays showed that the lentivirus‑mediated overexpression of CD97/ADGRE5 improved the inhibition of high glucose‑induced endothelial cell migration. In addition, using cytoskeleton staining, it was found that CD97 promoted membrane ruffling and lamellipodia formation. Cell division cycle 42, a small GTP‑binding protein, and its downstream factor, actin‑related protein 2, were involved in CD97‑induced actin reorganization in endothelial cells. Additionally, the use of transcription factor filter plate assays revealed that the nuclear translocation of signal transducer and activator of transcription 1 stimulated by high glucose contributed to the inhibited transcription of CD97. In conclusion, the present study established that the overexpression of CD97 improved high glucose‑induced dysfunction of endothelial cell migration. These findings provide insight to assist in identifying therapeutic targets with potential to ameliorate certain vascular complications of diabetes.
研究领域:
分子生物学
·
细胞生物学
·
糖尿病研究
·
血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2016
·
IF 3.418
Shuai Wang,Zewei Sun,Wenting Zhao,Zhen Wang,Mingjie Wu,Yanyun Pan,Hui Yan,Jianhua Zhu
CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-κB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-α and transcription factor NF-κB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-γ, was involved in the CD97 mediated NF-κB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-γ expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-γ expression and decreased LPS induced NF-κB activation. In conclusion, CD97 plays a negative role in LPS induced NF-κB activation and TNF-α secretion, partly through PPAR-γ upregulation.
研究领域:
免疫学
·
细胞生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2021
·Vol. 110
·期 3
·712-724
·
IF 3.368
Daren Liu,Jinhong Wu,Huanbing Zhu,Xiuliang Zhu,Yun Jin,Yuanquan Yu,Xiaoxiao Zhang
Despite progress in clinical treatment, microvascular invasion (MVI) remains a major factor for frequent recurrence and metastasis of hepatocellular carcinoma (HCC) after liver resection and surgery. Thus, this study constructed a target nanoplatform (αCD97-USPIO-Au-DDP) with magnetic field/near-infrared (NIR) light response using ultrasmall superparamagnetic iron oxide-gold nanoporous spheres (USPIO-Au) as multifunctional nanocarrier. Anticancer drug cisplatin (DDP) was loaded, and specifically expressed CD97 protein in MVI was taken as the therapeutic target. The αCD97-USPIO-Au-DDP showed favorable photothermal and stable properties under the NIR light at 808 nm wavelength. As suggested by in vitro and in vivo research, this composite nanopreparation could effectively reduce damage to normal organs and showed good biocompatibility. Excellent magnetic targeting function of nanocarrier and modification of αCD97 strengthened accumulation of composite nanodrug in tumor to inhibit tumor growth. This system may have important ramifications for treatment of MVI in HCC.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）