"Degenerative Lumbar Disc Disease Closely Linked to Acquired Aging Rather Than Genetics"

Jasaeng Spine and Joint Research Institute Senior Researcher Hong Jin-young Team
Gene Expression Changes in the Annulus Fibrosus Region of the Disc

DNMT3b enzyme was found to be the most involved in DNA methylation of degenerated discs.
[Photo by Jaseng Hospital of Korean Medicine]

[Asia Economy Reporter Lee Gwan-ju] A study has found that degenerative lumbar disc disease is more closely related to acquired aging than genetic factors.

The research team led by Senior Researcher Hong Jin-young at Jaseng Hospital of Korean Medicine Spine and Joint Research Institute announced on the 19th that they demonstrated the correlation between epigenetics and the mechanism of pain regulation in the back through observation and analysis of epigenetics-related tissues in an animal model induced with degenerative lumbar disc disease (lumbar intervertebral disc herniation).

Among the current theories explaining aging, the representative hypotheses are the genetic theory and epigenetics. The genetic theory views lifespan as determined by genetic makeup, whereas epigenetics considers that acquired changes in genes are possible due to environmental factors.

First, to create an animal model of degenerative lumbar disc disease, the research team made an incision in the abdomen of rats and created a hole in the disc (intervertebral disc) to remove the nucleus pulposus. Four weeks later, to understand the relationship between epigenetic changes and pain regulation mechanisms, they observed changes in the nucleus pulposus, a component of the disc, and the annulus fibrosus, a thick membrane surrounding it.

The observation was conducted by fluorescent staining of 5mC, a DNA component, and the pain receptor TRPV1 in green and red, respectively. 5mC is a representative marker indicating epigenetic changes, and TRPV1 is a protein responsible for the body’s sensation of pain.

Jinyoung Hong, Senior Researcher at Jaseng Spine and Joint Research Institute.

Analysis of the disc tissue showed that 5mC and TRPV1 expression were prominently observed in the annulus fibrosus area of the degenerative lumbar disc model. Notably, many cells showed dual staining with red and green combined into yellow, confirming the association between pain caused by degenerative lumbar disc disease and epigenetic changes. The research team explained that this indicates epigenetic involvement in the chronic pain process caused by degenerative lumbar disc disease.

Subsequently, the study also investigated enzymes that promote 'DNA methylation,' a representative mechanism of epigenetics. DNA methylation refers to the method by which cells regulate which genes among many are expressed. There are three enzymes that promote DNA methylation: DNMT1, DNMT3a, and DNMT3b, and the team stained and observed each enzyme.

As a result, DNMT3b was found to be most strongly expressed in the nucleus pulposus and annulus fibrosus regions of the degenerative lumbar disc model. The research team interpreted this to mean that most cells expressing 5mC also express DNMT3b, indicating that the DNMT3b enzyme plays the largest role in DNA methylation in the degenerated disc.

Senior Researcher Hong said, "This paper is significant as the first to address the correlation between epigenetic changes and pain regulation related to degenerative lumbar disc disease. Based on the specific antibodies and enzymes identified in this experiment, we plan to research new treatments and candidate substances targeting them," adding, "It will be an important key for future treatment methods and new drug research not only for degenerative lumbar disc disease but also for degenerative spinal diseases such as spinal stenosis and spondylolisthesis."

This research paper was recently published in the SCI(E)-level journal 'Cells' (IF=7.666).

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