title: Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration.
abstract: Post-natal skeletal stem cells expressing PRX1 (pnPRX1+) have been identified in the calvaria and in the axial skeleton. Here we characterize the location and functional capacity of the calvarial pnPRX1+cells. We found that pnPRX1+reside exclusively in the calvarial suture niche and decrease in number with age. They are distinct from preosteoblasts and osteoblasts of the sutures, respond to WNT signaling in vitro and in vivo by differentiating into osteoblasts, and, upon heterotopic transplantation, are able to regenerate bone. Diphtheria toxin A (DTA)-mediated lineage ablation of pnPRX1+cells and suturectomy perturb regeneration of calvarial bone defects and confirm that pnPRX1+cells of the sutures are required for bone regeneration. Orthotopic transplantation of sutures with traceable pnPRX1+cells into wild-type animals shows that pnPRX1+cells of the suture contribute to calvarial bone defect regeneration. DTA-mediated lineage ablation of pnPRX1+does not, however, interfere with calvarial development.
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wilk
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Shu-Chi A
authors.initials: SA
authors.lastname: Yeh
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA; Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Regenerative Bioscience Center, Rhodes Center for ADS, and College of Engineering, University of Georgia, Athens, GA 30602, USA.
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Mortensen
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Sasan
authors.initials: S
authors.lastname: Ghaffarigarakani
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA; University of Florida College of Dentistry, Gainesville, FL 32608, USA.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Lombardo
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Seyed Hossein
authors.initials: SH
authors.lastname: Bassir
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
authors.forename: Zahra A
authors.initials: ZA
authors.lastname: Aldawood
authors.affiliation: Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: lin@helix.mgh.harvard.edu.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: giuseppe_intini@hsdm.harvard.edu.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Intini
mesh_terms: D000375:Aging; D000818:Animals; D001861:Bone Regeneration; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D012886:Skull / Q000166:cytology* / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D018398:Homeodomain Proteins; C489936:Prrx1 protein, mouse
keywords: PRRX1; PRX1; calvarial bone regeneration; calvarial development; calvarial skeletal stem cells; stem cell niche