title: Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow.
abstract: Skeletal stem cells (SSCs) that are the major source of osteoblasts and adipocytes in adult bone marrow express leptin receptor (LepR). To test whether LepR regulates SSC function, we conditionally deleted Lepr from limb bone marrow stromal cells, but not from the axial skeleton or hypothalamic neurons, using Prx1-Cre. Prx1-Cre;Lepr(fl/fl) mice exhibited normal body mass and normal hematopoiesis. However, limb bones from Prx1-Cre;Lepr(fl/fl) mice exhibited increased osteogenesis, decreased adipogenesis, and accelerated fracture healing. Leptin increased adipogenesis and reduced osteogenesis by activating Jak2/Stat3 signaling in bone marrow stromal cells. A high-fat diet increased adipogenesis and reduced osteogenesis in limb bones from wild-type mice, but not from Prx1-Cre;Lepr(fl/fl) mice. This reflected local effects of LepR on osteogenesis and adipogenesis by bone marrow stromal cells and systemic effects on bone resorption. Leptin/LepR signaling regulates adipogenesis and osteogenesis by mesenchymal stromal cells in the bone marrow in response to diet and adiposity.
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yue
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Bo O
authors.initials: BO
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Issei S
authors.initials: IS
authors.lastname: Shimada
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: sean.morrison@utsouthwestern.edu.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D050156:Adipogenesis; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002454:Cell Differentiation; D059305:Diet, High-Fat; D005269:Femur / Q000473:pathology; D017102:Fracture Healing; D017353:Gene Deletion; D053614:Janus Kinase 2 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology; D009765:Obesity / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D054411:Receptors, Leptin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2