Matrix Metalloproteinase 12 is an Indicator of Intervertebral Disc Degeneration Co-expressed with Fibrotic Markers

Summary Objective Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. Design Transcriptional expression of fibrosis markers ( COL1A1, COL3A1, FN1 , HSP47 , MMP12, RASAL1) were analyzed in degenerated (D) and non-degenerated (ND) human nucleus pulposus (NP) and annulus fibrosus (AF) cells, along with traditional ( SOX9 , ACAN) and newly established degeneration markers ( CDH2 , KRT19, KRT18, FBLN1 , MGP , and COMP ). Protein expression was investigated by immunohistochemistry in human IVDs, and in rodent IVDs undergoing natural ageing or puncture-induced degeneration. Co-expression with myofibroblast markers was examined by double staining on human and rat specimens. Results Among the genes examined, D-NP showed significantly higher MMP12 expression along with lower KRT19 expression . Protein expression analysis revealed increased MMP12(+) cells in human D-IVD. Injury induced MMP12 positivity in peripheral rat NP and AF. Aged mouse NP also contained increased MMP12(+) cells. In addition, human D-NP and D-AF showed increased α-SMA(+) cells, indicating enhanced myofibroblast activity. MMP12 was found co-expressed with α-SMA, FSP1 and FAP-α in human and rat D-IVDs. Conclusions Our study suggests that in addition to a reduced KRT19 expression, an increased expression of MMP12 , a profibrotic mediator, is characteristic of disc degenerative changes. Co-expression study indicates an association of the increased MMP12 positivity with myofibroblast activity in D-IVDs. Overall, our findings implicate an impact of MMP12 in disc cell homeostasis. The precise role of MMP12 in IVD degeneration warrants further investigation.