Matrix metalloproteinases in pulpitis, chronic apical periodontitis and odontogenic jaw cysts

Matrix metalloproteinases (MMPs) form an enzyme family capable of degrading almost all extracellular matrix (ECM) and basement membrane (BM) components. They play an important role in normal tissue remodelling and growth, as well as in many destructive pathological conditions such as inflammation, tumour growth and metastasis. The expression of MMP-8 in cultured human mature pulpal cells and odontoblasts was evaluated with polymerase chain reaction-method (PCR). Mesenchyme-derived cells, pulp tissue cells and odontoblasts expressed MMP-8, which was down-regulated by transforming growth factor (TGF) in these cell cultures. Immunohistochemical staining revealed MMP-8 protein in the odontoblasts. These results suggest that MMP-8 may participate in dentin matrix organization during dentin formation. The presence of MMP-8 in inflammatory pulpal and periapical tissues and in root-canal exudate during root-canal treatment was further studied. Using immunohistochemistry, MMP-8 staining was detected in polymorphonuclear leukocytes (PMNs), macrophages and plasma cells in both pulpal and periapical lesions. MMP-8 has evidently a role in pulpal and periapical inflammation. MMP-8 levels in periapical exudate were significantly reduced during root canal treatment. Measuring MMP-8 levels in periapical exudate may be used as a biochemical indicator/ molecular marker to monitor the inflammatory activity and success in root canal treatment. Odontogenic keratocyst (KC) has special characteristics; its epithelium proliferates rapidly and detaches easily from connective tissue stroma, it recurs easily and forms daughter cysts. With this background, the differential expression of MMPs in odontogenic cysts was studied. The results revealed colocalization of MMP-2 and MMP-13 with laminin-5 (Ln-5) 2-chain in the KC basement membrane zone indicating that especially these MMPs may be responsible for the epithelial detachment of KC. In all odontogenic cysts, MMP-8 protein was detected not only in PMNs, but also macrophages and plasma cells by immunohistochemistry. In situ hybridization showed MMP-8 mRNA expression in the plasma cells of follicular cyst (FC). MMP-13 expression was also localized to plasma cells in periapical lesions, KCs and plasmacytoma (PLC) specimens by both immunohistochemical staining and in situ hybridization. Cultured multiple myeloma cells showed that the expression of MMP-8 and MMP-13 was enhanced by phorphol-12-myristate-13-acetate (PMA) and heparin combined with different cytokines like interleukin-6 (IL-6). Overall, these results show that MMPs play an important role in ECM and BM remodelling and destruction during dentin formation, inflammatory processes of pulpitis, apical periodontitis, and enlargement of odontogenic jaw cysts, as well as reflect the special characteristics of them.