Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration

Katarzyna Wilk; Shu-Chi A Yeh; Luke J Mortensen; Sasan Ghaffarigarakani; Courtney M Lombardo; Seyed Hossein Bassir; Zahra A Aldawood; Charles P Lin; Giuseppe Intini

doi:10.1016/j.stemcr.2017.03.002

Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration

Stem Cell Reports. 2017 Apr 11;8(4):933-946. doi: 10.1016/j.stemcr.2017.03.002. Epub 2017 Mar 30.

Authors

Katarzyna Wilk¹, Shu-Chi A Yeh², Luke J Mortensen³, Sasan Ghaffarigarakani¹, Courtney M Lombardo⁴, Seyed Hossein Bassir¹, Zahra A Aldawood¹, Charles P Lin⁵, Giuseppe Intini⁶

Affiliations

¹ Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.

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.

Keywords: PRRX1; PRX1; calvarial bone regeneration; calvarial development; calvarial skeletal stem cells; stem cell niche.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Aging
Animals
Bone Regeneration*
Gene Deletion
Homeodomain Proteins / analysis
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Male
Mice, Transgenic
Skull / cytology*
Skull / growth & development
Skull / physiology*
Skull / ultrastructure
Stem Cells / cytology*
Stem Cells / metabolism
Wnt Signaling Pathway

Substances

Homeodomain Proteins
Prrx1 protein, mouse

Grants and funding

R00 DE021069/DE/NIDCR NIH HHS/United States