A protein found in the backbone of a zebra fish that helps it heal itself as it gets older may actually regenerate your backbone too. It can get rid of those terrible back and neck pains caused by degenerative discs in your spinal cord. How? The protein is also present in humans and the fish model of regeneration can help us understand how it can be harnessed better by humans too. Which means bye-bye to painkillers and surgical interventions.
Considering the need to develop therapeutics that either stop disc degeneration or induce disc regeneration to get the healthy tissue back in the human spine, scientists at Pune’s Maharashtra Association for Cultivation of Science-Agharkar Research Institute (MACS-ARI) decided to study the zebrafish backbone. In aged fish, they found a protein, CCN2, that regenerates and heals discs in their backbone.
(From left) Amey Rayrikar, Ganesh Wagh and Dr Chinmoy Patra.
Accepted for publication in an international Journal Development, the findings are significant as this CCN2 protein is also present in humans. Dr Chinmoy Patra, senior scientist at ARI, says this regenerative potential of CCN2- (Cellular Communication Network factor 2) can be developed to treat degenerated human discs. Like humans, aged zebrafish develop natural disc degeneration at the cellular level. Dr Patra and his team found that the CCN2 protein promotes disc cell proliferation and survival.
The healing potential of new research
Nearly 60 per cent of the adult Indian population suffers from back or appendage pain due to disc degeneration. Most patients are prescribed painkillers, exercise/physical therapy, and lifestyle modifications, which provide symptomatic relief from the pain. Surgical treatments like spine fusion or disc replacement are done in severe cases.
What is intervertebral disc degeneration?
IVD degeneration (IVDD) is considered a major reason for back, neck and appendage pain, putting a considerable socio-economic burden on the clinical system. Historically, disc degeneration was believed to be associated only with ageing. However, recent studies suggest that it is also linked to genetic and health-related backgrounds. The human spine (backbone) consists of vertebrae, discs (also known as intervertebral discs or IVD) placed between two vertebrae, and a spinal cord running from the head to the end of the spine. In humans, with the progression of age, discs degenerate or become thinner naturally. This leads to lower back pain, neck pain, sciatica, disc hernia and others.
In Nature’s Bone Research journal (Aug 2021), researchers from the University of Bristol showed evidence of osteoporosis in aged zebrafish and said that as the global population ages, a substantial increase in morbidity due to degenerative diseases and back pain was expected. “This increase emphasises the importance of improving our understanding of the causes of IVDD and its relationship with other common degenerative conditions to revise or further develop novel therapeutic strategies,” they said.
Why use the zebrafish model?
Knowledge of disc pathophysiology is necessary to develop a novel pharmacological strategy to overcome back or appendage pain due to disc degeneration. Since humans can’t be used for experimental study, scientists use a variety of animal models. “Our present study used zebrafish (a small 2.5 to 3 cm long freshwater fish mostly abundant in the paddy field of eastern states of India) as a model organism. Zebrafish carry all the organs present in humans except the lungs and are genetically as well as physiologically pretty similar to humans. Further, similar to humans, their spines also consist of vertebrae, discs and a spinal cord, and discs degenerate. This evidence suggests zebrafish are a suitable animal model to identify pro-regenerative molecules that can induce regeneration in degenerated discs,” Dr Patra says.
How body processes can heal discs
Scientists sought to explore the processes involved in the maintenance of young discs and the pathophysiology in the aged discs, using zebrafish as a model organism. Their study shows that the structure of zebrafish discs is similar to human discs. Like humans, aged zebrafish develop natural disc degeneration at the cellular level. They found that the CCN2 protein promotes disc cell proliferation and survival. Most importantly, Dr Patra’s team discovered that in aged zebrafish, CCN2 treatment promotes regeneration in the degenerated discs and brings it back to a healthy state. “We found through genetic and biochemical approaches that CCN2a maintains the cell turnover in adult IVDs and can induce regeneration in degenerated IVDs. Our study shows that CCN2a is a crucial secreted molecule in IVD maintenance. This study enriches our understanding of the cellular and molecular mechanisms,” Dr Patra adds.
