title: A novel population of cells expressing both hematopoietic and mesenchymal markers is present in the normal adult bone marrow and is augmented in a murine model of marrow fibrosis.
abstract: Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent with this observation, mice expressing constitutively active parathyroid hormone (PTH)/PTH-related peptide receptors (PPR) in osteoblasts (PPR*Tg) display BM fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a double-mutant mouse expressing constitutively active PPR and green fluorescent protein (GFP) under the control of the type I collagen promoter (PPR*Tg/GFP) was generated. Confocal microscopy and flow cytometry revealed the presence of a cell population expressing GFP (GFP(+)) that was also positive for the hematopoietic marker CD45 in the BM of both PPR*Tg/GFP and control animals. This cell population was expanded in PPR*Tg/GFP. The existence of cells expressing both type I collagen and CD45 in the adult BM was confirmed by IHC and fluorescence-activated cell sorting. An analysis of total RNA extracted from sorted GFP(+)CD45(+) cells showed that these cells produced type I collagen and PTH/PTH-related peptide receptor and receptor activator for NF-κB mRNAs, further supporting their features of being both mesenchymal and hematopoietic lineages. Similar cells, known as fibrocytes, are also present in pathological fibroses. Our findings, thus, indicate that the BM is a permissive microenvironment for the differentiation of fibrocyte-like cells and raise the possibility that these cells could contribute to the pathogenesis of BM fibrosis.
authors.affiliation: Endocrine Unit, the Department of Medicine, Faculty of Medical Sciences, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ohishi
authors.forename: Wanida
authors.initials: W
authors.lastname: Ono
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ono
authors.forename: Richa
authors.initials: R
authors.lastname: Khatri
authors.forename: Marilena
authors.initials: M
authors.lastname: Marzia
authors.forename: Emma K
authors.initials: EK
authors.lastname: Baker
authors.forename: Sierra H
authors.initials: SH
authors.lastname: Root
authors.forename: Tremika Le-Shan
authors.initials: TL
authors.lastname: Wilson
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kronenberg
authors.forename: Hector L
authors.initials: HL
authors.lastname: Aguila
authors.forename: Louise E
authors.initials: LE
authors.lastname: Purton
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D024042:Collagen Type I; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D055728:Primary Myelofibrosis / Q000378:metabolism / Q000473:pathology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1; D049452:Green Fluorescent Proteins