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FoxA2+ 长时程干细胞群体对于损伤后生长板软骨再生是必需的。

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

机构信息

Department of Biology, 134 Mugar Life Sciences Building, Northeastern University, 360 Huntington Ave, Boston, MA, 02115, USA.

Centre for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA.

出版信息

Nat Commun. 2022 May 6;13(1):2515. doi: 10.1038/s41467-022-30247-1.

DOI:10.1038/s41467-022-30247-1
PMID:35523895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076650/
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.

摘要

长骨的纵向生长是通过软骨内骨化完成的，其结构是骺板或生长板，由与软骨细胞功能相关的形态不同的区域组成：静止区、增殖区和肥大区。静止区是富含干细胞的区域，它产生生长板，并具有再生能力以应对损伤。我们发现了一群 FoxA2+长骨干/基质细胞，位于静止区的顶部，靠近次级骨化中心，与先前表征的 PTHrP+干细胞不同。与 PTHrP+细胞相比，FoxA2+细胞表现出更高的克隆形成能力和寿命。FoxA2+细胞在出生后早期（P0-P28）表现出双重成骨-软骨-祖细胞活性，并且在 P28 之后具有成软骨潜能。当生长板受伤时，FoxA2+细胞会在创伤的刺激下扩增，并产生骺板软骨以促进生长板组织再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/c225a7faea85/41467_2022_30247_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/8e3b7d588cd4/41467_2022_30247_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/006853f846b4/41467_2022_30247_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/20c1d3cbe63f/41467_2022_30247_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/b64ea40b7359/41467_2022_30247_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/08cc43f20aed/41467_2022_30247_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/15c8c9327990/41467_2022_30247_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/c225a7faea85/41467_2022_30247_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/8e3b7d588cd4/41467_2022_30247_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/54e1a6212bb9/41467_2022_30247_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/3628ac8c8bb4/41467_2022_30247_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/006853f846b4/41467_2022_30247_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/20c1d3cbe63f/41467_2022_30247_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/b64ea40b7359/41467_2022_30247_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/08cc43f20aed/41467_2022_30247_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/15c8c9327990/41467_2022_30247_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ebc/9076650/c225a7faea85/41467_2022_30247_Fig9_HTML.jpg

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