Biochemical and physicochemical determinations in a premyelin fraction obtained by zonal centrifugation in normal mouse and in dysmyelinating mutants (quaking, shiverer, and myelin-deficient)

1986 ◽  
Vol 4 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Jean-Marie Bourre ◽  
Françoise Boiron ◽  
Claude Cassagne ◽  
Odile Dumont ◽  
François Leterrier ◽  
...  
Keyword(s):  
Normal Mouse ◽  
Myelin Deficient ◽  
Dysmyelinating Mutants

Synchrotron radiation X-rays demonstrate small cerebral vessels in normal mouse and variations under ischemia in rat

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S558-S558
Author(s):  
Masahiro Tamaki ◽  
Takashi Mizobe ◽  
Keiji Kidoguchi ◽  
Junnji Koyama ◽  
Takeshi Kondoh ◽  
...  
Keyword(s):  
Synchrotron Radiation ◽  
Normal Mouse ◽  
Cerebral Vessels ◽  
X Rays

scholarly journals OP0036 IL-6 ACTIVATES YES-ASSOCIATED PROTEIN (YAP) IN FIBROBLASTS AND INDUCES YAP-SNAIL COMPLEX FORMATION TO DRIVE SYNOVIAL LINING PATHOLOGY IN INFLAMMATORY ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 19.1-19
Author(s):  
R. Symons ◽  
F. Colella ◽  
F. Collins ◽  
A. Roelofs ◽  
C. De Bari
Keyword(s):  
Transcription Factor ◽  
Complex Formation ◽  
Inflammatory Arthritis ◽  
Normal Mouse ◽  
Joint Destruction ◽  
Proximity Ligation Assay ◽  
Synovial Lining ◽  
Arthritis Severity ◽  
Marginal Erosions

Background:In rheumatoid arthritis (RA), the fibroblast-like synoviocytes (FLS) in synovial lining become invasive and cause joint destruction. The molecular mechanisms underpinning this pathogenic FLS phenotype are incompletely understood. The FLS descend from Growth differentiation factor 5 (Gdf5)-expressing joint interzone cells in the embryo, and we showed that conditional ablation of the transcriptional co-activator Yes associated protein (Yap) in Gdf5-lineage cells prevents synovial lining hyperplasia after traumatic cartilage injury in mice [1].Objectives:Here, we investigated a potential role for Yap in pathogenic FLS in immune-mediated inflammatory arthritis.Methods:Immunohistochemistry was used to detect Yap in human RA synovium and Yap, Snail and Ctgf in mouse synovium following antigen-induced arthritis (AIA). To determine the effect of Yap knockout (KO) in synovial stromal cells, AIA was induced in Gdf5-Cre;tdTomato;Yapfl/fl (Yap cKO) and Gdf5-Cre;tdTomato;Yapwt/wt (control) mice, or in Pdgfrα-CreER;Yapfl/fl (Yap ciKO, targeting Pdgfrα-expressing fibroblasts) and Yapfl/fl or YapWT/fl (control) mice after adult tamoxifen induction. Yap KO in both models was confirmed by immunohistochemistry. After nine days, arthritis severity was determined by histological scoring of synovial lining hyperplasia, immune infiltrates, cellular exudate, and marginal erosions. TdTomato+ Gdf5-lineage cells in synovium were quantified. In vitro, Yap reporter cells were treated with inflammatory cytokines to evaluate their ability to stimulate Yap-induced GFP expression by flow cytometry. Snail overexpression, siRNA-mediated Yap knockdown, and IL-6/sIL-6R stimulation were performed on normal mouse FLS, AIA-FLS or human RA-FLS, and cell invasion through a matrigel-coated transwell was quantified. A proximity ligation assay was utilised to detect Yap/Snail complex formation.Results:Average expression levels of Yap (p<0.0001), its transcription factor partner Snail (p=0.002), and their downstream target Ctgf (p=0.0003), were increased in mouse synovium after AIA (n=5), and Yap was highly expressed by FLS in human RA synovium. Yap cKO mice (n=24) showed a significantly decreased arthritis severity (p=0.002) after AIA compared to controls (n=22), with significant reductions in synovial lining hyperplasia (p<0.001), synovial immune cell infiltrates (p=0.026) and marginal erosions (p=0.002). Similarly, Yap ciKO mice (n=6) showed a significant decrease in arthritis score (p=0.039) after AIA compared to controls (n=9). However, both control mice (p<0.001) and Yap cKO mice (p<0.001) showed an extensive expansion of tdTomato+ Gdf5-lineage synovial cells after AIA, with no significant difference between control and Yap cKO mice. In vitro, Yap knockdown prevented IL-6/sIL-6R-induced invasion of normal mouse FLS (p=0.037) and decreased the invasiveness of AIA-FLS (p=0.0057). Using Yap reporter cells, we found that Yap was activated by IL-6/sIL-6R (p=0.016), but not TNFα or IL-1β. Finally, IL-6/sIL-6R treatment of normal mouse FLS (p=0.033) or human RA-FLS (p=0.036) induced Yap-Snail complex formation, and Yap knockdown prevented FLS invasion induced by Snail overexpression (p=0.027).Conclusion:These data demonstrate that via activation by IL-6, and co-operation with the transcription factor Snail, Yap acts as a key modulator of the invasive and destructive phenotype of FLS in inflammatory arthritis. Therapeutic targeting of Yap could reduce joint destruction in RA.References:[1]A. J. Roelofs et al., “Joint morphogenetic cells in the adult mammalian synovium,” Nat. Commun., vol. 8, no. May, p. 15040, 2017. DOI: 10.1136/annrheumdis-2018-213799Acknowledgements:This work was funded by the Medical Research Council (MR/L020211/1 and MR/L022893/1) and Versus Arthritis (20775 and 21156).Disclosure of Interests:None declared

scholarly journals Vanadate stimulation of insulin release in normal mouse islets.

1991 ◽  
Vol 266 (32) ◽  
pp. 21649-21656
Author(s):  
A.Q. Zhang ◽  
Z.Y. Gao ◽  
P. Gilon ◽  
M. Nenquin ◽  
G. Drews ◽  
...  
Keyword(s):  
Insulin Release ◽  
Normal Mouse ◽  
Mouse Islets ◽  
Stimulation Of

Intrinsic mineralization defect inHyp mouse osteoblasts

1998 ◽  
Vol 275 (4) ◽  
pp. E700-E708 ◽  
Author(s):  
Z. S. Xiao ◽  
M. Crenshaw ◽  
R. Guo ◽  
T. Nesbitt ◽  
M. K. Drezner ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Disease ◽  
Normal Mouse ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Diffusible Factor ◽  
Murine Homologue ◽  
Mineralization Defect ◽  
Inactivating Mutations

X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3′ Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb- Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37 ± 6 vs. 1,484 ± 68 counts ⋅ min−1 ⋅ μg protein−1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits mineralization of extracellular matrix in vitro.

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