Gli1 labels progenitors during chondrogenesis in postnatal mice

Skeletal growth promoted by endochondral ossification is tightly coordinated by self-renewal and differentiation of chondrogenic progenitors. Emerging evidence has shown that multiple skeletal stem cells (SSCs) participate in cartilage formation. However, as yet, no study has reported the existence...

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Bibliographic Details
Published in:EMBO reports 2024-04, Vol.25 (4), p.1773-1791
Main Authors: Li, Boer, Yang, Puying, Shen, Fangyuan, You, Chengjia, Wu, Fanzi, Shi, Yu, Ye, Ling
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Cartilage
Cell Differentiation
Chondrocytes
Chondrogenesis - genetics
EMBO11
EMBO34
Life Sciences
Mice
Osteogenesis
Zinc Finger Protein GLI1 - genetics
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Summary:Skeletal growth promoted by endochondral ossification is tightly coordinated by self-renewal and differentiation of chondrogenic progenitors. Emerging evidence has shown that multiple skeletal stem cells (SSCs) participate in cartilage formation. However, as yet, no study has reported the existence of common long-lasting chondrogenic progenitors in various types of cartilage. Here, we identify Gli1 + chondrogenic progenitors (Gli1 + CPs), which are distinct from PTHrP + or FoxA2 + SSCs, are responsible for the lifelong generation of chondrocytes in the growth plate, vertebrae, ribs, and other cartilage. The absence of Gli1 + CPs leads to cartilage defects and dwarfishness phenotype in mice. Furthermore, we show that the BMP signal plays an important role in self-renewal and maintenance of Gli1 + CPs. Deletion of Bmpr1α triggers Gli1 + CPs quiescence exit and causes the exhaustion of Gli1 + CPs, consequently disrupting columnar cartilage. Collectively, our data demonstrate that Gli1 + CPs are common long-term chondrogenic progenitors in multiple types of cartilage and are essential to maintain cartilage homeostasis. Synopsis Gli1 + chondrogenic progenitors maintained by BMP signal are responsible for the lifelong generation of chondrocytes in various types of cartilage and are indispensable for cartilage homeostasis. Gli1 + chondrogenic progenitors (Gli1 + CPs) are responsible for the lifelong generation of chondrocytes in the growth plate, vertebrae, ribs. Ablation of Gli1 + CPs leads to severe cartilage defects and growth retardation. Deletion of BMPR1A leads to the exhaustion of Gli1 + CPs and abnormalities of cartilage formation. Gli1 + chondrogenic progenitors maintained by BMP signal are responsible for the lifelong generation of chondrocytes in various types of cartilage and are indispensable for cartilage homeostasis.
ISSN:1469-3178
1469-221X
1469-3178
DOI:10.1038/s44319-024-00093-x