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The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression

Author

Listed:
  • Jian Huang

    (Rush University Medical Center)

  • Lan Zhao

    (Rush University Medical Center)

  • Yunshan Fan

    (Rush University Medical Center)

  • Lifan Liao

    (Rush University Medical Center)

  • Peter X. Ma

    (University of Michigan)

  • Guozhi Xiao

    (Rush University Medical Center)

  • Di Chen

    (Rush University Medical Center)

Abstract

Osteoarthritis (OA) is a common, painful disease. Currently OA is incurable, and its etiology largely unknown, partly due to limited understanding of OA as a whole-joint disease. Here we report that two homologous microRNAs, miR-204 and miR-211, maintain joint homeostasis to suppress OA pathogenesis. Specific knockout of miR-204/-211 in mesenchymal progenitor cells (MPCs) results in Runx2 accumulation in multi-type joint cells, causing whole-joint degeneration. Specifically, miR-204/-211 loss-of-function induces matrix-degrading proteases in articular chondrocytes and synoviocytes, stimulating articular cartilage destruction. Moreover, miR-204/-211 ablation enhances NGF expression in a Runx2-dependent manner, and thus hyper-activates Akt signaling and MPC proliferation, underlying multiplex non-cartilaginous OA conditions including synovial hyperplasia, osteophyte outgrowth and subchondral sclerosis. Importantly, miR-204/-211-deficiency-induced OA is largely rescued by Runx2 insufficiency, confirming the miR-204/-211-Runx2 axis. Further, intraarticular administration of miR-204-expressing adeno-associated virus significantly decelerates OA progression. Collectively, miR-204/-211 are essential in maintaining healthy homeostasis of mesenchymal joint cells to counteract OA pathogenesis.

Suggested Citation

  • Jian Huang & Lan Zhao & Yunshan Fan & Lifan Liao & Peter X. Ma & Guozhi Xiao & Di Chen, 2019. "The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10753-5
    DOI: 10.1038/s41467-019-10753-5
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    Cited by:

    1. Kosei Nagata & Hironori Hojo & Song Ho Chang & Hiroyuki Okada & Fumiko Yano & Ryota Chijimatsu & Yasunori Omata & Daisuke Mori & Yuma Makii & Manabu Kawata & Taizo Kaneko & Yasuhide Iwanaga & Hideki N, 2022. "Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Lan Zhao & Yumei Lai & Hongli Jiao & Jian Huang, 2024. "Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Ming-liang Ji & Hua Jiang & Zhuang Li & Rui Geng & Jun Zheng Hu & Yu Cheng Lin & Jun Lu, 2022. "Sirt6 attenuates chondrocyte senescence and osteoarthritis progression," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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