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

Author

Listed:
  • 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
    Chemistry, and Medicine, Boston University)

  • 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)

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.

Suggested Citation

  • 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 & Y, 2022. "A FoxA2+ long-term stem cell population is necessary for growth plate cartilage regeneration after injury," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30247-1
    DOI: 10.1038/s41467-022-30247-1
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    References listed on IDEAS

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    1. Phillip T. Newton & Lei Li & Baoyi Zhou & Christoph Schweingruber & Maria Hovorakova & Meng Xie & Xiaoyan Sun & Lakshmi Sandhow & Artem V. Artemov & Evgeny Ivashkin & Simon Suter & Vyacheslav Dyachuk , 2019. "A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate," Nature, Nature, vol. 567(7747), pages 234-238, March.
    2. Koji Mizuhashi & Wanida Ono & Yuki Matsushita & Naoko Sakagami & Akira Takahashi & Thomas L. Saunders & Takashi Nagasawa & Henry M. Kronenberg & Noriaki Ono, 2018. "Resting zone of the growth plate houses a unique class of skeletal stem cells," Nature, Nature, vol. 563(7730), pages 254-258, November.
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    Cited by:

    1. Chee Ho H’ng & Shanika L. Amarasinghe & Boya Zhang & Hojin Chang & Xinli Qu & David R. Powell & Alberto Rosello-Diez, 2024. "Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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