The problem of intervertebral disk degeneration (IDD) has emerged as a critical health concern worldwide, particularly due to an aging population. Chronic lower back pain resulting from IDD significantly impacts the quality of life and mobility for millions of individuals. Recent innovative research led by a team of scientists at Nanjing University School of Life Sciences offers promising developments in this area with a novel "glycan glue" that repairs damaged spinal disks.

Overview of the Study

Conducted in collaboration with the University of Macau and the First Affiliated Hospital of Soochow University, this research introduces a glucomannan-based solution aimed at restoring disk health through the enhancement of a key protein, Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8). The study, titled An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration, was published in Nature Communications (2025) and is referenced under DOI: 10.1038/s41467-025-58946-5.

Understanding MFG-E8 and Its Role

The research team identified significant variations in MFG-E8 levels during the progression of IDD. MFG-E8 is a secreted glycoprotein critical for maintaining the integrity of intervertebral disks through its structural properties:

  • N-terminal EGF-like domain: Binds to integrin receptors.
  • RGD motif: Facilitates cell adhesion.
  • C-terminal F5/8-type domain: Interacts with phospholipids and glycans, enabling MFG-E8 to act as a molecular bridge in cellular interactions.

This multifunctionality allows MFG-E8 to play a significant role in remodeling the extracellular matrix (ECM), which is vital for maintaining a balanced tissue microenvironment. The findings suggest that the loss of MFG-E8 leads to degeneration of intervertebral disks, prompting the need for therapeutic replacement.

Glycan Glue Innovation

The study developed a unique glucomannan ester, referred to as GMOC, that mimics the structure of natural glycosaminoglycans (GAGs) and exhibits exceptional resistance to enzymatic degradation. The effectiveness of GMOC in ameliorating IDD is demonstrated through its ability to:

  • Enhance endogenous levels of MFG-E8 within the degenerative microenvironment.
  • Regulate nucleus pulposus cell function.
  • Slow the progression of intervertebral disk degeneration.

Comparative Analysis of GMOC and Hyaluronic Acid

Hyaluronic acid (HA) is typically utilized in therapies to remediate the degenerative microenvironment, yet it suffers from rapid degradation, particularly due to the enzyme hyaluronidase-2 (HYAL-2) prevalent in IDD. GMOC, in contrast, demonstrates stability at the site of implantation, making it a potentially more effective treatment option.

Material Stability Mechanism
GMOC High resistance to enzymatic degradation Enhances MFG-E8, regulates ECM remodeling
Hyaluronic Acid Rapidly degraded by HYAL-2 Acts as a filler but lacks regulatory support

Validation Through Animal Models

The research team conducted experiments on rat and rabbit models simulating various clinical scenarios. The findings revealed:

  • In a rat IDD model: GMOC injections successfully alleviated early-stage degeneration by improving tissue hydration, preserving disk height, and maintaining overall tissue integrity over a four-week period.
  • In a rabbit partial disk resection model: GMOC filling remarkably preserved tissue integrity for up to six weeks post-surgery.

Challenges and Future Directions

Despite the promising results, the researchers acknowledged limitations, particularly the challenge of utilizing MFG-E8 knockout rat models for more thorough mechanistic studies. This situation arises due to overlapping gene coding regions that impact hyaluronic acid synthesis.

To advance this research further, the team intends to collaborate with international researchers to address these challenges and better understand MFG-E8's regulatory mechanisms in tissue repair.

Conclusion

This innovative research demonstrates the potential of enzyme-resistant glycan glue as a powerful therapeutic agent for intervertebral disk degeneration. By restoring disk integrity through the enhancement of MFG-E8, GMOC offers a promising avenue for improving patient outcomes in chronic lower back pain and mobility challenges associated with IDD.

References

Yu Liu et al. (2025). An enzyme-proof glycan glue for extracellular matrix to ameliorate intervertebral disc degeneration. Nature Communications. DOI: 10.1038/s41467-025-58946-5.

This document is based on findings provided by Nanjing University School of Life Sciences. For further reading, please refer to the original article here.