A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury
Shanmugam Muruganandan, Rachel Pierce, Dian Teguh, Rocio Fuente Perez, Nicole Bell, Brandon Nguyen, Katherine Hohl, Brian D. Snyder, Mark W. Grinstaff, Hannah Alberico, Dori C. Woods, Yiwei Kong, Corneliu Sima, Sanket Bhagat, Kailing Ho, Vicki Rosen, Laura W. Gamer, Andreia Ionescu
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.