1.COMP-Angiopoietin-1 Stimulates Synovial Proliferation but Suppresses Osteoclast by Enhancing Angiogenesis and Osteoblast Maturation in Collagen-Induced Arthritis.
Yong Geun JEONG ; Hyun Ok KIM ; Hye Song LIM ; Young Sool HAH ; Hee Young CHO ; Jiahua YU ; Byung Hyun PARK ; Gou Young KOH ; Sang Il LEE
Journal of Rheumatic Diseases 2012;19(2):82-90
OBJECTIVE: Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA). METHODS: A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed. RESULTS: AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group. CONCLUSION: COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.
Adenoviridae
;
Angiogenesis Inducing Agents
;
Angiopoietin-1
;
Animals
;
Arthritis
;
Arthritis, Experimental
;
Arthritis, Rheumatoid
;
Blood Vessels
;
Cartilage
;
Collagen Type I
;
Extracellular Matrix Proteins
;
Glycoproteins
;
Inflammation
;
Integrin-Binding Sialoprotein
;
Joints
;
Lifting
;
Mice
;
Osteoblasts
;
Osteoclasts
;
Osteogenesis
;
Osteopontin
;
Osteoprotegerin
;
Synovial Membrane
;
Transcription Factors
2.Expression of hypoxia-inducible factor-1 in mice infected with Toxoplasma gondii during pregnancy
Yu-lu ZENG ; Sa XUE ; Xiang-lian BI ; Ling-xin YAN ; Jun YANG ; Da-yi ZHANG ; Yong-song GOU ; Xiao-yin FU ; Deng-yu LIU
Chinese Journal of Schistosomiasis Control 2021;33(6):615-622
Objective To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. Methods Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1α, HIF-1β and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1α and VEGF mRNA expression was examined. In addition, and the HIF-1α expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. Results Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1α (F = 132.6, P < 0.05) and HIF-1β mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1α (F = 111.5, P < 0.05) and HIF-1β mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1α and HIF-1β mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1α expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1α expression was detected in mouse uterine specimens. Conclusions HIF-1α expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1α inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes.
3. Study on urine metabolomics of left-behind children with vitamin D deficiency under 1 year old in Zunyi area based on nuclear magnetic resonance
Li LEI ; Yu CHENG ; Yanan SONG ; Yunfeng XIANG ; Hongjiao JIN ; Huiling SONG ; Enjin GOU ; Qing LI ; Xuqin WANG ; Limei LUO ; Yong LIN ; Bo HUANG
Chinese Journal of Applied Clinical Pediatrics 2019;34(20):1565-1569
Objective:
To explore the characteristic changes in urinary metabolites in left-behind children with vitamin D deficiency under 1 year old in Zunyi area by metabolomic nuclear magnetic resonance (NMR) in order to provide new biomarkers for early diagnosis of vitamin D deficiency.
Methods:
From January to August 2018, blood tests and urine collection were carried out on the left-behind children under 1 year old in Fenggang county, Bozhou district and Zheng′an county under Zunyi city by stratified sampling.Forty children diagnosed as a vitamin D deficiency were selected as a vitamin D deficiency group, and 40 children with normal urine test were selected as a healthy control group.For urine sampling, SIMCA-P+ software was applied to analyze the integral value of hydrogen spectrogram by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) was used to distinguish the difference in urine metabolites between two groups of the left-behind children.Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to screen different metabolites.
Results:
The serum level of 25-hydroxy vitamin D[25-(OH)D][(32.0±3.6) nmol/L ] in the healthy control group was higher than that in the vitamin D deficiency group[(15.8±2.3) nmol/L], and the difference was statistically significant (
4.Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.
Chen CHU ; Lu YU ; Joelle HENRY-BERGER ; Yan-Fei RU ; Ayhan KOCER ; Alexandre CHAMPROUX ; Zhi-Tong LI ; Miao HE ; Sheng-Song XIE ; Wu-Bin MA ; Min-Jie NI ; Zi-Mei NI ; Yun-Li GUO ; Zhao-Liang FEI ; Lan-Tao GOU ; Qiang LIU ; Samanta SHARMA ; Yu ZHOU ; Mo-Fang LIU ; Charlie Degui CHEN ; Andrew L EAMENS ; Brett NIXON ; Yu-Chuan ZHOU ; Joël R DREVET ; Yong-Lian ZHANG
Asian Journal of Andrology 2020;22(6):590-601
The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5