title: Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells.
abstract: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment. Controversy exists on N-cadherin's role in support of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is required for normal marrow microarchitecture and for hematopoiesis. To determine whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin resulted in an age-dependent bone phenotype, ultimately characterized by decreased mineralized bone, but no difference in steady-state HSC numbers or function at any time tested, and normal recovery from myeloablative injury. Intermittent parathyroid hormone (PTH) treatment is well established as anabolic to bone and to increase marrow HSCs through microenvironmental interactions. Lack of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of PTH treatment. This report demonstrates that osteoblastic N-cadherin is not required for regulation of steady-state hematopoiesis, HSC response to myeloablation, or for rapid expansion of HSCs through intermittent treatment with PTH.
authors.affiliation: Endocrine Division, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Bromberg
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Frisch
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Weber
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Porter
authors.forename: Roberto
authors.initials: R
authors.lastname: Civitelli
authors.forename: Laura M
authors.initials: LM
authors.lastname: Calvi
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D015519:Bone Density / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D010281:Parathyroid Hormone; D012333:RNA, Messenger