title: Hematopoietic stem cells give rise to osteo-chondrogenic cells.
abstract: Repair of bone fracture requires recruitment and proliferation of stem cells with the capacity to differentiate to functional osteoblasts. Given the close association of bone and bone marrow (BM), it has been suggested that BM may serve as a source of these progenitors. To test the ability of hematopoietic stem cells (HSCs) to give rise to osteo-chondrogenic cells, we used a single HSC transplantation paradigm in uninjured bone and in conjunction with a tibial fracture model. Mice were lethally irradiated and transplanted with a clonal population of cells derived from a single enhanced green fluorescent protein positive (eGFP+) HSC. Analysis of paraffin sections from these animals showed the presence of eGFP+ osteocytes and hypertrophic chondrocytes. To determine the contribution of HSC-derived cells to fracture repair, non-stabilized tibial fracture was created. Paraffin sections were examined at 7 days, 2 weeks and 2 months after fracture and eGFP+ hypertrophic chondrocytes, osteoblasts and osteocytes were identified at the callus site. These cells stained positive for Runx-2 or osteocalcin and also stained for eGFP demonstrating their origin from the HSC. Together, these findings strongly support the concept that HSCs generate bone cells and suggest therapeutic potentials of HSCs in fracture repair.
authors.affiliation: Department of Veterans Affairs Medical Center, Ralph H. Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Meenal
authors.initials: M
authors.lastname: Mehrotra
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Williams
authors.forename: Makio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Amanda C
authors.initials: AC
authors.lastname: LaRue
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology; D020219:Chondrogenesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D017102:Fracture Healing; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis; D013977:Tibia / Q000293:injuries*; D013978:Tibial Fractures / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; C485184:enhanced green fluorescent protein; D015675:Osteocalcin; D049452:Green Fluorescent Proteins