title: Diabetes impairs the interactions between long-term hematopoietic stem cells and osteopontin-positive cells in the endosteal niche of mouse bone marrow.
abstract: Hematopoietic stem cells (HSCs) are maintained, and their division/proliferation and quiescence are regulated in the microenvironments, niches, in the bone marrow. Although diabetes is known to induce abnormalities in HSC mobilization and proliferation through chemokine and chemokine receptors, little is known about the interaction between long-term HSCs (LT-HSCs) and osteopontin-positive (OPN) cells in endosteal niche. To examine this interaction, LT-HSCs and OPN cells were isolated from streptozotocin-induced diabetic and nondiabetic mice. In diabetic mice, we observed a reduction in the number of LT-HSCs and OPN cells and impaired expression of Tie2, β-catenin, and N-cadherin on LT-HSCs and β1-integrin, β-catenin, angiopoietin-1, and CXCL12 on OPN cells. In an in vitro coculture system, LT-HSCs isolated from nondiabetic mice exposed to diabetic OPN cells showed abnormal mRNA expression levels of Tie2 and N-cadherin. Conversely, in LT-HSCs derived from diabetic mice exposed to nondiabetic OPN cells, the decreased mRNA expressions of Tie2, β-catenin, and N-cadherin were restored to normal levels. The effects of diabetic or nondiabetic OPN cells on LT-HSCs shown in this coculture system were confirmed by the coinjection of LT-HSCs and OPN cells into bone marrow of irradiated nondiabetic mice. Our results provide new insight into the treatment of diabetes-induced LT-HSC abnormalities and suggest that the replacement of OPN cells may represent a novel treatment strategy.
authors.affiliation: Department of Orthopedic Surgery. Sapporo Medical University Faculty of Medicine, Sapporo, Japan, and.
authors.forename: Hironori
authors.initials: H
authors.lastname: Chiba
authors.forename: Koji
authors.initials: K
authors.lastname: Ataka
authors.forename: Kousuke
authors.initials: K
authors.lastname: Iba
authors.forename: Kanna
authors.initials: K
authors.lastname: Nagaishi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Mineko
authors.initials: M
authors.lastname: Fujimiya
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche; D013997:Time Factors
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C506896:Spp1 protein, mouse; D053495:Osteopontin
keywords: Tie2; intrabone marrow-bone marrow transplantation; osteoblastic niche