The Role of Dot1l in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone

JBMR Plus

Nancy B Schwartz¹  Judith G Henry¹  Miriam S Domowicz¹  Stephanie Y Jo² 

[1] Department of Pediatrics University of Chicago Chicago IL USA;Department of Radiology University of Pennsylvania Philadelphia PA USA;

关键词: EPIGENETICS;    GENETIC ANIMAL MODELS;    OSTEOARTHRITIS;    OSTEOPOROSIS;   

DOI  :  10.1002/jbm4.10254

来源: DOAJ

【 摘 要 】

ABSTRACT Osteoarthritis and osteoporosis are widely prevalent and have far‐reaching public health implications. There is increasing evidence that epigenetics, in particular, histone 3 lysine 79 methyltransferase DOT1L, plays an important role in the cartilage and bone biology. In this study, we evaluated the role of Dot1l in the articular cartilage, growth plate, and trabecular bone utilizing conditional KO mouse models. We generated chondrocyte‐specific constitutive and inducible conditional Dot1l KO mouse lines using Col2a1‐Cre and Acan‐CreER systems. Prenatal deletion of Dot1l in mouse chondrocytes led to perinatal mortality, accelerated ossification, and dysregulation of Col10a1 expression. Postnatal deletion of Dot1l in mouse chondrocytes resulted in trabecular bone loss decreased extracellular matrix production, and disruption of the growth plate. In addition, pharmacological inhibition of DOT1L in a progeria mouse model partially rescued the abnormal osseous phenotype. In conclusion, Dot1l is important in maintaining the growth plate, extracellular matrix production, and trabecular bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

【 授权许可】

Unknown