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

• Published in: eLife Vol. 10
• Main Authors: Wei, Yulong, Sun, Hao, Gui, Tao, Yao, Lutian, Zhong, Leilei, Yu, Wei, Heo, Su-Jin, Han, Lin, Dyment, Nathaniel A, Liu, Xiaowei Sherry, Zhang, Yejia, Koyama, Eiki, Long, Fanxin, Zgonis, Miltiadis H, Mauck, Robert L, Ahn, Jaimo, Qin, Ling
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.06.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Age; Animals; Cartilage diseases; Cell culture; Cell Lineage; Cell Proliferation; Degeneration; Developmental Biology; Disease Models, Animal; Gli1; Hedgehog protein; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Humans; Injuries; Knee; Ligaments; lineage tracing; Male; Menisci, Tibial - metabolism; Menisci, Tibial - pathology; Menisci, Tibial - surgery; Meniscus; meniscus injury; mesenchymal progenitor; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; Mice, Knockout; Osteoarthritis; Osteoarthritis, Knee - genetics; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - pathology; Osteoarthritis, Knee - prevention & control; Progenitor cells; Signal Transduction; Stem cells; Stem Cells and Regenerative Medicine; Swine; Swine, Miniature; Tibial Meniscus Injuries - genetics; Tibial Meniscus Injuries - metabolism; Tibial Meniscus Injuries - pathology; Tibial Meniscus Injuries - surgery; Time Factors; Wound Healing; Zinc Finger Protein GLI1 - genetics; Zinc Finger Protein GLI1 - metabolism; mouse; stem cells; developmental biology; osteoarthritis; regenerative medicine; mesenchymal progenitor; lineage tracing; Gli1; meniscus injury
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.62917

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 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.