The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.

Abstract

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

• Authors: Yulong Wei, Hao Sun, Tao Gui, Lutian Yao, Leilei Zhong, Wei Yu, Su-Jin Heo, Lin Han, Nathaniel A Dyment, Xiaowei Sherry Liu, Yejia Zhang, Eiki Koyama, Fanxin Long, Miltiadis H Zgonis, Robert L Mauck, Jaimo Ahn, Ling Qin
• Journal: eLife (Elife) Vol. 10 (06 04 2021) ISSN: 2050-084X [Electronic] England
• PMID: 34085927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2021, Wei et al.

Chemical References

• Gli1 protein, mouse
• Hedgehog Proteins
• Zinc Finger Protein GLI1

Topics

• Animals
• Cell Lineage
• Cell Proliferation
• Disease Models, Animal
• Hedgehog Proteins (genetics, metabolism)
• Humans
• Male
• Menisci, Tibial (metabolism, pathology, surgery)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Mice, Knockout
• Osteoarthritis, Knee (genetics, metabolism, pathology, prevention & control)
• Signal Transduction
• Swine
• Swine, Miniature
• Tibial Meniscus Injuries (genetics, metabolism, pathology, surgery)
• Time Factors
• Wound Healing
• Zinc Finger Protein GLI1 (genetics, metabolism)
• Mice