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An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration

Author

Listed:
  • Yu Liu

    (University of Macau)

  • Tzuwei Chao

    (University of Macau)

  • Yuwei Li

    (University of Macau
    University of Macau)

  • Peng Peng

    (The First Affiliated Hospital of Soochow University)

  • Gaoran Ge

    (The First Affiliated Hospital of Soochow University)

  • Dechun Geng

    (The First Affiliated Hospital of Soochow University)

  • Lei Dong

    (Nanjing University
    National Resource Center for Mutant Mice
    Nanjing University)

  • Chunming Wang

    (University of Macau
    University of Macau
    University of Macau)

Abstract

Intervertebral disc degeneration (IDD) remains a global healthcare challenge. Here, by analyzing clinical samples, we discover the loss of milk fat globule-EGF factor 8 (MFG-E8) from the nucleus pulposus (NP) tissue—along with increased enzymatic breakdown of glycosaminoglycans (GAGs)—as an overlooked factor for IDD development. Repairing the degraded NP extracellular matrix (ECM) with a structurally-mimicking glycan glue to enrich MFG-E8 may counter the degeneration. Accordingly, we synthesize a glucomannan octanoate (GMOC) with robust resistance to ECM-cleaving enzymes, which forms assemblies with MFG-E8 to maintain a healthy NP cell phenotype. GMOC injected into the degenerated intervertebral disc enriches MFG-E8 in situ, leading to NP tissue regeneration in a rat and a rabbit model, which represent two clinical scenarios of pre-surgical intervention and post-surgical regeneration of IDD, respectively. In summary, we report enriching MFG-E8 in ECM with a glycan glue as a mechanism to promote NP regeneration for IDD treatment.

Suggested Citation

  • Yu Liu & Tzuwei Chao & Yuwei Li & Peng Peng & Gaoran Ge & Dechun Geng & Lei Dong & Chunming Wang, 2025. "An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58946-5
    DOI: 10.1038/s41467-025-58946-5
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    References listed on IDEAS

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    1. Yanxian Feng & Ruoyu Mu & Zhenzhen Wang & Panfei Xing & Junfeng Zhang & Lei Dong & Chunming Wang, 2019. "A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Rikinari Hanayama & Masato Tanaka & Keiko Miwa & Azusa Shinohara & Akihiro Iwamatsu & Shigekazu Nagata, 2002. "Identification of a factor that links apoptotic cells to phagocytes," Nature, Nature, vol. 417(6885), pages 182-187, May.
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