Zebrafish protein could hold the answer to chronic back pain

Indian scientists find a protein in zebrafish could help regenerate spinal discs, which is the only way disc related pain could be cured

MDDTimes

A study by Agharkar Research Institute (ARI), Pune, India, says that a protein found in zebrafish could induce disc regeneration, which is the only way spinal disc related back pain could be cured in humans.

Spinal discs (intervertebral discs or IVDs) degenerate due to aging and overuse, which causes low back, neck, and appendage pain. Pain relievers or anti-inflammatories are currently used and disc replacement or disc fusion surgery is performed in severe cases. However, no medical procedures or treatments are known to suppress disc degeneration or induce disc regeneration.

Against that backdrop, the study assumes significance. It found that zebrafish IVDs possess distinct and non-overlapping zones of cell proliferation and cell death. In zebrafish, cellular communication network factor 2a (ccn2a) is expressed in notochord and IVDs. Although IVD development appears normal in ccn2a mutants, the adult mutant IVDs exhibit decreased cell proliferation and increased cell death leading to IVD degeneration. Moreover, Ccn2a overexpression promotes regeneration through accelerating cell proliferation and suppressing cell death in wild-type aged IVDs.

MDDTimes
Researchers at ARI; source – GoI

The study says that mechanistically, Ccn2a maintains IVD homeostasis and promotes IVD regeneration by enhancing outer annulus fibrosus cell proliferation and suppressing nucleus pulposus cell death through augmenting FGFR1-SHH signalling.

“These findings reveal that Ccn2a plays a central role in IVD homeostasis and regeneration, which could be exploited for therapeutic intervention in degenerated human discs,” said the study.

The study, which used zebrafish as a model organism, is the first in vivo study showing that it is possible to induce disc regeneration by activating an endogenous signalling cascade. The scientists also found that the Ccn2a-FGFR1-SHH signalling cascade takes a positive role in disc maintenance and augmenting disc regeneration.

The study used genetic and biochemical approaches and is likely to help design a novel strategy to suppress disc degeneration or induce disc regeneration in human discs.

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