title: Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties.
abstract: Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took a combined approach of high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties.
authors.affiliation: Department of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA anju.singh@nih.gov lglimche@med.cornell.edu.
authors.forename: Anju
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Rheumatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Chantel
authors.initials: C
authors.lastname: Lester
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Drapp
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Dorothy Z
authors.initials: DZ
authors.lastname: Hu
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA anju.singh@nih.gov lglimche@med.cornell.edu.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.affiliation: Abide Therapeutics, San Diego, CA 92121, USA.
authors.forename: Dallas
authors.initials: D
authors.lastname: Jones
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D057166:High-Throughput Screening Assays; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000000981:diagnostic imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*; D060245:Tetraspanin 29 / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; C554870:Cd9 protein, mouse; D060245:Tetraspanin 29; D015720:5'-Nucleotidase
keywords: Osteoblast; Osteochondroprogenitor; Skeletal stem cell