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

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 , plays an important role in the cartilage and bone biology. In this study, we evaluated the role of in the articular cartilage, growth plate, and trabecular bone utilizing conditional KO mouse models. We generated chondrocyte-specific constitutive and inducible conditional KO mouse lines using - and systems. Prenatal deletion of in mouse chondrocytes led to perinatal mortality, accelerated ossification, and dysregulation of expression. Postnatal deletion of 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, is important in maintaining the growth plate, extracellular matrix production, and trabecular bone. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.