FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3209445994> ?p ?o ?g. }

• W3209445994 endingPage "101376" @default.
• W3209445994 startingPage "101376" @default.
• W3209445994 abstract "Notch2tm1.1Ecan mice, which harbor a mutation replicating that found in Hajdu-Cheney syndrome, exhibit marked osteopenia because of increased osteoclast number and bone resorption. Hairy and enhancer of split 1 (HES1) is a Notch target gene and a transcriptional modulator that determines osteoclast cell fate decisions. Transcript levels of Hes1 increase in Notch2tm1.1Ecan bone marrow-derived macrophages (BMMs) as they mature into osteoclasts, suggesting a role in osteoclastogenesis. To determine whether HES1 is responsible for the phenotype of Notch2tm1.1Ecan mice and the skeletal manifestations of Hajdu-Cheney syndrome, Hes1 was inactivated in Ctsk-expressing cells from Notch2tm1.1Ecan mice. Ctsk encodes the protease cathepsin K, which is expressed preferentially by osteoclasts. We found that the osteopenia of Notch2tm1.1Ecan mice was ameliorated, and the enhanced osteoclastogenesis was reversed in the context of the Hes1 inactivation. Microcomputed tomography revealed that the downregulation of Hes1 in Ctsk-expressing cells led to increased bone volume/total volume in female mice. In addition, cultures of BMMs from CtskCre/WT;Hes1Δ/Δ mice displayed a decrease in osteoclast number and size and decreased bone-resorbing capacity. Moreover, activation of HES1 in Ctsk-expressing cells led to osteopenia and enhanced osteoclast number, size, and bone resorptive capacity in BMM cultures. Osteoclast phenotypes and RNA-Seq of cells in which HES1 was activated revealed that HES1 modulates cell-cell fusion and bone-resorbing capacity by supporting sealing zone formation. In conclusion, we demonstrate that HES1 is mechanistically relevant to the skeletal manifestation of Notch2tm1.1Ecan mice and is a novel determinant of osteoclast differentiation and function." @default.
• W3209445994 created "2021-11-08" @default.
• W3209445994 creator A5004430702 @default.
• W3209445994 creator A5066151926 @default.
• W3209445994 creator A5077417367 @default.
• W3209445994 creator A5090353903 @default.
• W3209445994 date "2021-12-01" @default.
• W3209445994 modified "2023-09-27" @default.
• W3209445994 title "Hairy and enhancer of split 1 is a primary effector of NOTCH2 signaling and induces osteoclast differentiation and function" @default.
• W3209445994 cites W1518638756 @default.
• W3209445994 cites W1551331657 @default.
• W3209445994 cites W1787104679 @default.
• W3209445994 cites W1964739634 @default.
• W3209445994 cites W1967502057 @default.
• W3209445994 cites W1967929323 @default.
• W3209445994 cites W1967967197 @default.
• W3209445994 cites W1971439989 @default.
• W3209445994 cites W1972623289 @default.
• W3209445994 cites W1976390169 @default.
• W3209445994 cites W1984311005 @default.
• W3209445994 cites W1993419851 @default.
• W3209445994 cites W1998943231 @default.
• W3209445994 cites W2005533362 @default.
• W3209445994 cites W2006044067 @default.
• W3209445994 cites W2011767107 @default.
• W3209445994 cites W2017372504 @default.
• W3209445994 cites W2018245903 @default.
• W3209445994 cites W2019213459 @default.
• W3209445994 cites W2021339292 @default.
• W3209445994 cites W2022412700 @default.
• W3209445994 cites W2025044532 @default.
• W3209445994 cites W2028951998 @default.
• W3209445994 cites W2037792397 @default.
• W3209445994 cites W2048875368 @default.
• W3209445994 cites W2057141194 @default.
• W3209445994 cites W2057907407 @default.
• W3209445994 cites W2058383340 @default.
• W3209445994 cites W2066749771 @default.
• W3209445994 cites W2076382804 @default.
• W3209445994 cites W2077816235 @default.
• W3209445994 cites W2078284356 @default.
• W3209445994 cites W2081379880 @default.
• W3209445994 cites W2082612168 @default.
• W3209445994 cites W2091007034 @default.
• W3209445994 cites W2096388724 @default.
• W3209445994 cites W2096425957 @default.
• W3209445994 cites W2098085126 @default.
• W3209445994 cites W2102278945 @default.
• W3209445994 cites W2103850847 @default.
• W3209445994 cites W2108234281 @default.
• W3209445994 cites W2111239144 @default.
• W3209445994 cites W2117025246 @default.
• W3209445994 cites W2128289981 @default.
• W3209445994 cites W2128737197 @default.
• W3209445994 cites W2129396527 @default.
• W3209445994 cites W2130913446 @default.
• W3209445994 cites W2131980428 @default.
• W3209445994 cites W2134526812 @default.
• W3209445994 cites W2140739060 @default.
• W3209445994 cites W2143813009 @default.
• W3209445994 cites W2144925860 @default.
• W3209445994 cites W2149827038 @default.
• W3209445994 cites W2150058505 @default.
• W3209445994 cites W2151297367 @default.
• W3209445994 cites W2153795402 @default.
• W3209445994 cites W2158727573 @default.
• W3209445994 cites W2170081920 @default.
• W3209445994 cites W2178572083 @default.
• W3209445994 cites W2179438025 @default.
• W3209445994 cites W2179817751 @default.
• W3209445994 cites W2271758870 @default.
• W3209445994 cites W2346299808 @default.
• W3209445994 cites W2468502072 @default.
• W3209445994 cites W2583682522 @default.
• W3209445994 cites W2603182464 @default.
• W3209445994 cites W2611762732 @default.
• W3209445994 cites W2616238416 @default.
• W3209445994 cites W2747127020 @default.
• W3209445994 cites W2762775515 @default.
• W3209445994 cites W2769815612 @default.
• W3209445994 cites W2790760441 @default.
• W3209445994 cites W2884681152 @default.
• W3209445994 cites W2890791786 @default.
• W3209445994 cites W2941963533 @default.
• W3209445994 cites W2943555235 @default.
• W3209445994 cites W2965683649 @default.
• W3209445994 cites W2970147514 @default.
• W3209445994 cites W3034574868 @default.
• W3209445994 cites W3035534921 @default.
• W3209445994 cites W3119097972 @default.
• W3209445994 cites W3127236158 @default.
• W3209445994 cites W4255059920 @default.
• W3209445994 cites W876816957 @default.
• W3209445994 doi "https://doi.org/10.1016/j.jbc.2021.101376" @default.
• W3209445994 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34742737" @default.
• W3209445994 hasPublicationYear "2021" @default.
• W3209445994 type Work @default.
• W3209445994 sameAs 3209445994 @default.

• next