A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury

Shanmugam Muruganandan, Rachel Pierce, Dian Astari Teguh, Rocio Fuente Perez, Nicole Bell, Brandon Nguyen, Katherine Hohl, Brian D. Snyder, Mark W. Grinstaff, Hannah Alberico, Dori Woods, Yiwei Kong, Corneliu Sima, Sanket Bhagat, Kailing Ho, Vicki Rosen, Laura Gamer and Andreia M. Ionescu ()
Additional contact information
Shanmugam Muruganandan: 134 Mugar Life Sciences Building, Northeastern University
Rachel Pierce: 134 Mugar Life Sciences Building, Northeastern University
Dian Astari Teguh: Beth Israel Deaconess Medical Center
Rocio Fuente Perez: University of Oviedo
Nicole Bell: New York University College of Dentistry
Brandon Nguyen: Moderna Therapeutics
Katherine Hohl: Beth Israel Deaconess Medical Center
Brian D. Snyder: Boston Children’s Hospital
Mark W. Grinstaff: Chemistry, and Medicine, Boston University
Hannah Alberico: 134 Mugar Life Sciences Building, Northeastern University
Dori Woods: 134 Mugar Life Sciences Building, Northeastern University
Yiwei Kong: 134 Mugar Life Sciences Building, Northeastern University
Corneliu Sima: Infection, and Immunity, Harvard School of Dental Medicine
Sanket Bhagat: Ultragenyx Pharmaceutical
Kailing Ho: Harvard School of Dental Medicine
Vicki Rosen: Harvard School of Dental Medicine
Laura Gamer: Harvard School of Dental Medicine
Andreia M. Ionescu: 134 Mugar Life Sciences Building, Northeastern University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Longitudinal bone growth, achieved through endochondral ossification, is accomplished by a cartilaginous structure, the physis or growth plate, comprised of morphologically distinct zones related to chondrocyte function: resting, proliferating and hypertrophic zones. The resting zone is a stem cell-rich region that gives rise to the growth plate, and exhibits regenerative capabilities in response to injury. We discovered a FoxA2+group of long-term skeletal stem cells, situated at the top of resting zone, adjacent the secondary ossification center, distinct from the previously characterized PTHrP+ stem cells. Compared to PTHrP+ cells, FoxA2+ cells exhibit higher clonogenicity and longevity. FoxA2+ cells exhibit dual osteo-chondro-progenitor activity during early postnatal development (P0-P28) and chondrogenic potential beyond P28. When the growth plate is injured, FoxA2+ cells expand in response to trauma, and produce physeal cartilage for growth plate tissue regeneration.

Date: 2022
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DOI: 10.1038/s41467-022-30247-1

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