Ligamentum flavum fibrosis and hypertrophy: Molecular pathways, cellular mechanisms, and future directions

Hypertrophy of ligamentum flavum (LF), along with disk protrusion and facet joints degeneration, is associated with the development of lumbar spinal canal stenosis (LSCS). Of note, LF hypertrophy is deemed as an important cause of LSCS. Histologically, fibrosis is proved to be the main pathology of LF hypertrophy. Despite the numerous studies explored the mechanisms of LF fibrosis at the molecular and cellular levels, the exact mechanism remains unknown. It is suggested that pathophysiologic stimuli such as mechanical stress, aging, obesity, and some diseases are the causative factors. Then, many cytokines and growth factors secreted by LF cells and its surrounding tissues play different roles in activating the fibrotic response. Here, we summarize the current status of detailed knowledge available regarding the causative factors, pathology, molecular and cellular mechanisms implicated in LF fibrosis and hypertrophy, also focusing on the possible avenues for anti-fibrotic strategies.