The Emerging Role of MMP12 in the Oral Environment

Abstract

Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.

Design and Synthesis of Novel Ultralong-Acting Peptides as EDP-EBP Interaction Inhibitors for Pulmonary Fibrosis Treatment

“…Interestingly, the results of differential gene expression analyses revealed a significant upregulation of MMP-12 in L XJ‑02 -treated lungs compared to BLM-treated lungs (Figures F, S4A). MMP-12 is known to degrade a variety of ECM proteins, including elastin, type IV collagen, FN, and laminin. ,,,− A previous study reported that BLM induces high expression of MMP-12 in mouse lungs, and inhibiting MMP-12 significantly reverses alveolar remodeling . However, based on our findings, we hypothesized that L XJ‑02 could promote the degradation of ECM components by upregulating the macrophage-MMP-12 axis.…”

“…Previous studies have emphasized the significance of MMP-12 inhibitors in ameliorating inflammation and fibrosis. 32,33,40,42 However, our findings highlight the central role of L XJ-02 in stimulating the proteolytic degradation of ECM and reversing PF by increasing the level of expression of MMP-12 in the lungs. This establishes a virtuous cycle that intensifies the clearance of ECM but diminishes various lung fibrotic response.…”

“…On one hand, it facilitates the clearance of fibrillar tissue by digesting ECM. On the other hand, the elastase activity of MMP-12 can generate various levels of EDPs, which are known to be involved in tissue remodeling and fibrotic disease through their EDP-receptor interaction. ,,,,− Inhibiting MMP-12 is considered an important strategy for improving inflammation resolution and reducing fibrosis. ,,− However, if appropriate molecules could neutralize the downstream effects of EDPs, MMP-12 could be considered as a beneficial factor for clearing scarred tissue in PF. Our study reveals a novel therapeutic mechanism, distinct from previously disclosed methods for treating PF.…”