title: The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow.
abstract: The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kuznetsov
authors.forename: Mara
authors.initials: M
authors.lastname: Riminucci
authors.forename: Navid
authors.initials: N
authors.lastname: Ziran
authors.forename: Takeo W
authors.initials: TW
authors.lastname: Tsutsui
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsi
authors.forename: Laura
authors.initials: L
authors.lastname: Calvi
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kronenberg
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
authors.forename: Pamela Gehron
authors.initials: PG
authors.lastname: Robey
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1