title: Overexpression of Bmi1 in Lymphocytes Stimulates Skeletogenesis by Improving the Osteogenic Microenvironment.
abstract: To investigate whether overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by improving the osteogenic microenvironment, we examined the skeletal phenotype of EμBmi1 transgenic mice with overexpression of Bmi1 in lymphocytes. The size of the skeleton, trabecular bone volume and osteoblast number, indices of proliferation and differentiation of bone marrow mesenchymal stem cells (BM-MSCs) were increased significantly, ROS levels were reduced and antioxidative capacity was enhanced in EμBmi1 mice compared to WT mice. In PTHrP1-84 knockin (Pthrp(KI/KI)) mice, the expression levels of Bmi1 are reduced and potentially can mediate the premature osteoporosis observed. We therefore generated a Pthrp(KI/KI) mice overexpressing Bmi1 in lymphocytes and compared them with Pthrp(KI/KI) and WT littermates. Overexpression of Bmi1 in Pthrp(KI/KI) mice resulted in a longer lifespan, increased body weight and improvement in skeletal growth and parameters of osteoblastic bone formation with reduced ROS levels and DNA damage response parameters. Our results demonstrate that overexpression of Bmi1 in lymphocytes can stimulate osteogenesis in vivo and partially rescue defects in skeletal growth and osteogenesis in Pthrp(KI/KI) mice. These studies therefore indicate that overexpression of Bmi1 in lymphocytes can stimulate skeletogenesis by inhibiting oxidative stress and improving the osteogenic microenvironment.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, China.|The State Key Laboratory of Reproductive Medicine, the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Xichao
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Reproductive Medicine, the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiuliang
authors.initials: X
authors.lastname: Dai
authors.affiliation: The State Key Laboratory of Reproductive Medicine, the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Reproductive Medicine, the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.|Department of Fundamentals of Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ji
authors.affiliation: The Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Karaplis
authors.affiliation: The Department of Medicine, McGill University, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
authors.affiliation: The Department of Medicine, McGill University, Montreal, Canada.|Rosalind &Morris Goodman Cancer Research Center, Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Xiangjiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Reproductive Medicine, the Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D004249:DNA Damage; D004260:DNA Repair; D006706:Homeostasis; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010012:Osteogenesis; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; C489421:Bmi1 protein, mouse; D044162:Parathyroid Hormone-Related Protein; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1