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Updated: May 30, 2026

Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
Midkine expression in human periapical granulomas
Keisuke Hatori1, Osamu Takeichi, Bunnai Ogiso
1Nihon University Graduate School of Dentistry, Nihon, Japan.
Introduction:
The expression of midkine (MK), a heparin-binding growth factor, is increased in various human tumors, making it a promising tumor marker and target for tumor therapy. MK is also related to the regulation of the development and etiology of chronic or autoimmune diseases; however, the involvement of MK in apical periodontitis has never been examined. This study compared the localization of MK-expressing cells and MK messenger RNA expression in periapical granulomas with healthy gingival tissues.
Methods:
Periapical lesions were removed surgically from chronic apical periodontitis patients, and serial tissue sections were stained with hematoxylin-eosin. The lesions diagnosed as periapical granulomas pathologically were examined by immunohistochemistry using human MK monoclonal antibodies. MK messenger RNA expression was also detected using real-time polymerase chain reaction analysis. Healthy gingival tissues were analyzed in the same manner.
Results:
MK was expressed by inflammatory cells, such as macrophages, lymphocytes, and neutrophils, as well as by endothelial cells in periapical granulomas but not in healthy gingival tissues. The MK-expressing inflammatory cells were seen adjacent to blood vessels, which contained MK-expressing endothelial cells, suggesting the interaction of MK among these cells during the process of inflammatory cell infiltration. Quantitative analysis of MK messenger RNA expression revealed that periapical granulomas expressed significantly more MK than healthy gingival tissues.
Conclusions:
These findings suggest that MK is involved in the pathogenesis of periapical granulomas.
Insights
Midkine (MK) is elevated in periapical granulomas, found on inflammatory cells and endothelial cells. This suggests midkine plays a role in the development of apical periodontitis.
Area of Science:
- Oral biology
- Immunology
- Pathology
Background:
- Midkine (MK) is a growth factor implicated in various human tumors and autoimmune diseases.
- Its role in apical periodontitis, a chronic inflammatory dental condition, remains unexplored.
Purpose of the Study:
- To investigate the presence and localization of midkine (MK) and its messenger RNA (mRNA) in periapical granulomas.
- To compare MK expression in periapical granulomas with healthy gingival tissues.
Main Methods:
- Surgical removal and pathological diagnosis of periapical granulomas from chronic apical periodontitis patients.
- Immunohistochemistry and real-time polymerase chain reaction (PCR) to detect MK protein and mRNA expression.
- Analysis of healthy gingival tissues as controls.
Main Results:
- Midkine (MK) was expressed by inflammatory cells (macrophages, lymphocytes, neutrophils) and endothelial cells within periapical granulomas.
- MK expression was notably absent in healthy gingival tissues.
- Periapical granulomas exhibited significantly higher MK mRNA levels compared to healthy tissues.
Conclusions:
- Midkine (MK) is present in periapical granulomas, associated with inflammatory and endothelial cells.
- These findings indicate midkine (MK) involvement in the pathogenesis of apical periodontitis.

