biostudies-literatureYu JNational Institute of Arthritis and Musculoskeletal and Skin DiseasesUConn HealthNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSEuropean CommissionNIAMS NIH HHS101376https://www.ebi.ac.uk/biostudies/studies/S-EPMC8633688biostudies-literatureUnknown297(6)Notch2^tm1.1Ecan 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 Notch2^tm1.1Ecan 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 Notch2^tm1.1Ecan mice and the skeletal manifestations of Hajdu-Cheney syndrome, Hes1 was inactivated in Ctsk-expressing cells from Notch2^tm1.1Ecan mice. Ctsk encodes the protease cathepsin K, which is expresThe Journal of biological chemistryHairy and enhancer of split 1 is a primary effector of NOTCH2 signaling and induces osteoclast differentiation and function.PMC8633688AR078149R01 AR078149DK045227R01 DK045227AR072987R01 AR072987Schilling LCanalis EYu JEller TfalseHairy and enhancer of split 1 is a primary effector of NOTCH2 signaling and induces osteoclast differentiation and function.Notch2^tm1.1Ecan 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 Notch2^tm1.1Ecan 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 Notch2^tm1.1Ecan mice and the skeletal manifestations of Hajdu-Cheney syndrome, Hes1 was inactivated in Ctsk-expressing cells from Notch2^tm1.1Ecan mice. Ctsk encodes the protease cathepsin K, which is expres2021-01-01T00:00:00Z2021 Dec2026-05-09T12:59:47.666Z2022-02-11T14:17:09.577ZS-EPMC86336883474273710.1016/j.jbc.2021.101376