THE ROLE OF ELASTIN-DERIVED PEPTIDES IN THE PATHOPHYSIOLOGY OF LIGAMENTUM FLAVUM HYPERTROPHY

Abstract

Lumbar spinal stenosis (LSS) results from the narrowing of the spinal canal, primarily attributed to hypertrophied ligamentum flavum (LF), leading to symptoms like radiculopathy. Surgical intervention, while effective, carries risks prompting exploration of alternative therapies. Elastin-derived peptides (EDPs), known for their pathological roles in other elastic tissues, have not been studied in LF. This study hypothesized that EDPs contribute to LF hypertrophy by regulating matrixmetalloproteinase-2 (MMP-2) expression, chondrogenesis, calcification, and macrophage polarization. A rat model mimicked human LF hypertrophy, showing elastin degradation and increased MMP-2 expression, implicating the expected generation of tissue-derived EDPs. EDPs extracted from human LF differed between hypertrophied and healthy LF. In vitro studies revealed EDPs' capacity to boost MMP-2 activity, chondrogenesis, osteogenesis, and provoke mixed macrophage polarization. These findings imply EDPs' involvement in LF hypertrophy, suggesting them as a promising therapeutic target for LSS management.