Degenerative spinal disease is a condition in which patients experience pain, stiffness and a loss of mobility due to arthritis in the bones, ligaments, and discs of the spine.
The condition occurs due to wear and tear from mechanical forces (such as lifting, twisting and bending and the vibration from operating vehicles and machinery) and the breakdown of spinal discs, joints and tissues as we age.
Treatments for degenerative spinal disease include non-surgical options such as back support devices, lifestyle changes (such as moving differently) and physical therapy.
Surgical treatments include lumbar decompression and/or fusion, in which arthritic bone, ligament, and discs are removed in order to relieve compression on the nerves and spinal cord, which can reduce pain and increase stability.
A new Mass General Brigham research study, led by spine neurosurgeons Muhamed Hadzipasic, MD, PhD, and Ganesh Shankar MD, PhD and published in Nature Biomedical Engineering takes a closer look at how mechanical forces drive changes to the spine that lead to degenerative spinal disease and identifies a signaling pathway that could potentially be targeted as a new, non-surgical treatment.
We asked Drs. Shankar and Hadzipasic to tell us more about the study:
Q. What problem or question were you investigating with this study?
We sought to understand how mechanical forces acting on the spine activate specific molecular signaling pathways that drive the harmful changes seen in spinal ligaments, particularly the thickening and stiffening (fibrosis) of the ligamentum flavum that contributes to nerve compression and spinal stenosis (a narrowing of the spine that can lead to nerve compression and pain).
Q. What was unique about your approach?
Our multidisciplinary approach combined clinical samples from human patients, advanced computer modeling (finite element analysis), and innovative laboratory experiments. We designed a custom bioreactor to apply realistic mechanical forces to ligament tissues outside the body.
This allowed us to precisely mimic what happens in the spine and to see how these mechanical forces activate molecular pathways, such as the ROCK signaling pathway, that lead to fibrosis.
The ROCK pathway is crucial in regulating various cellular processes, including cell shape, motility, proliferation, and survival, particularly by influencing the cytoskeleton.
Q. What (if any) challenges or obstacles did you encounter along the way?
We encountered several challenges. Chief among them was the difficulty of measuring the exact mechanical forces experienced by the ligamentum flavum inside the human body.
Since direct measurement is impossible in living patients, we relied on sophisticated computer simulations to estimate these forces.
Another challenge was maintaining the health and responsiveness of the ligament tissue in the lab environment, which required careful handling and innovative experimental setups.
Q. What did you find?
We found that mechanical stress by itself is enough to trigger the activation of the ROCK signaling pathway in the ligament cells. This pathway prompts the cells to become myofibroblasts — specialized cells that produce scar-like tissue and cause the ligament to stiffen and thicken.
We also discovered that when we blocked the ROCK pathway using specific inhibitors, these harmful changes were significantly reduced. This confirmed that the ROCK pathway is both necessary for and central to this process.
Q. What are the implications for treatment of degenerative spinal disease?
We believe these findings open the door to the possibility of new, non-surgical treatments for degenerative spinal disease.
Rather than relying solely on surgery to remove thickened ligament tissue, we envision that ROCK inhibitors could one day be used to slow or prevent the progression of fibrosis in the spine — offering patients an effective, disease-modifying therapy.
Q. What are the next steps?
Our next step is to test ROCK inhibitors in animal models to evaluate their safety and long-term effects in living systems. These studies are essential before we can consider clinical trials in human patients.
Ultimately, we hope this line of research will lead to non-surgical treatments that preserve spinal health and prevent nerve compression caused by ligament thickening.
Q. What collaborations within the system (and beyond) made this study possible?
This work was made possible through extensive collaboration between clinicians, scientists, and engineers.
We brought together spine surgeons from Massachusetts General Hospital, tissue engineers from the Massachusetts Institute of Technology, and experts in tissue micromechanics from Boston University.
This close teamwork across disciplines allowed us to connect the mechanics of the whole spine with molecular changes in ligament tissue.
Q. What’s one thing people should know about keeping their spines healthy?
We would advise that keeping the spine healthy requires maintaining flexibility, strength, and proper posture.
Regular physical activity, maintaining a healthy weight, and avoiding chronic excessive mechanical strain on the spine are helpful in reducing harmful stresses on spinal ligaments — and may help prevent the degenerative processes we have studied.
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