title: Parathyroid hormone enhances hematopoietic expansion via upregulation of cadherin-11 in bone marrow mesenchymal stromal cells.
abstract: Parathyroid hormone (PTH) stimulates hematopoiesis in mouse models. The involvement of osteoblasts in this process has been well investigated; however, the effects of PTH on human hematopoiesis and bone marrow mesenchymal stromal cells (BM-MSCs) are unclear. Here, we show that BM-MSCs contribute to the hematopoiesis-stimulating effects of PTH via upregulation of cadherin-11 (CDH11). When culture-expanded human BM-MSCs were stimulated with PTH, their ability to expand cocultured CD34(+) hematopoietic progenitor cells (HPCs) was enhanced. Furthermore, when PTH-treated BM-MSCs were subcutaneously implanted into NOD/SCID mice, the induction of hematopoietic cells was enhanced. Culture-expanded human BM-MSCs expressed CDH11, and the level of CDH11 expression increased following PTH stimulation. Depletion of CDH11 expression in BM-MSCs using small interfering RNA abolished the enhancement of HPC expansion by PTH-treated BM-MSCs. In lethally irradiated mice that underwent BM transplantation, CDH11 expression in BM-MSCs was higher and survival was better in PTH-treated mice than in control mice. The number of hematopoietic cells in BM and the number of red blood cells in peripheral blood were higher in PTH-treated mice than in control mice. Our results demonstrate that PTH stimulates hematopoiesis through promoting the upregulation of CDH11 expression in BM-MSCs, at least in part. PTH treatment may be an effective strategy to enhance the ability of BM-MSCs to support hematopoiesis.
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yao
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Masako
authors.initials: M
authors.lastname: Miura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Iwasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Terutoshi
authors.initials: T
authors.lastname: Hishita
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Higashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kaneko
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D055785:Gene Knockdown Techniques; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D064593:Heterografts; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010281:Parathyroid Hormone / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D010281:Parathyroid Hormone; D034741:RNA, Small Interfering; C086960:osteoblast cadherin
keywords: Bone marrow mesenchymal stromal/stem cells; Cadherin-11; Hematopoiesis; Parathyroid hormone