title: Osteoblast precursor cells are found in CD34+ cells from human bone marrow.
abstract: It is known that osteoblast precursor cells are found in the low-density mononuclear (LDMN) fraction of human bone marrow (BM) aspirates. The purpose of this study was to investigate whether CD34, a hematopoietic progenitor cell marker, is present on osteoblast progenitor cells. LDMN, CD34+, and CD34- cells were cultured under conditions that promote growth and differentiation of mineral-secreting osteoblasts in a limiting dilution manner. With LDMN cells, osteoblast progenitor cells were found at an average frequency of 1/36,000 cells. With CD34- cells, osteoblast progenitor frequency remained at an average of 1/33,000, similar to LDMN cells. With CD34+ selected cells, osteoblast progenitor frequency increased to an average of 1/5,000. This osteoblast progenitor frequency is maintained in sorted CD34+/CD38+ cells. The osteoblasts generated from CD34+ cells were morphologically normal, and expression of skeletal-specific alkaline phosphatase and osteonectin increased upon differentiation induced by dexamethasone (DEX) treatment. Ultrastructurally, these CD34+ cell-derived osteoblasts displayed osteoblast-specific features. Functionally, these CD34+ cell-derived osteoblasts differentiated with DEX treatment, increased the level of cyclic adenosine monophosphate in response to parathyroid hormone stimulation, increased the level of alkaline phosphatase activity, and increased mineral secretion. These results demonstrate that osteoblast progenitor cells are enriched in the CD34+ cell population from BM and that these progenitor cells can differentiate into functional osteoblasts in culture.
authors.affiliation: Amgen Inc., Thousand Oaks, California 91320, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Hunt
authors.forename: M
authors.initials: M
authors.lastname: McElvain
authors.forename: T
authors.initials: T
authors.lastname: Black
authors.forename: S
authors.initials: S
authors.lastname: Kaufman
authors.forename: E S
authors.initials: ES
authors.lastname: Choi
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins; D008903:Minerals / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000032:analysis; D010006:Osteoblasts / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure; D015676:Osteonectin / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D008903:Minerals; D015676:Osteonectin; D010281:Parathyroid Hormone; D003907:Dexamethasone; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1