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Updated: Apr 12, 2026
Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
Cathepsin K Inhibitor Regulates Inflammation and Bone Destruction in Experimentally Induced Rat Periapical Lesions
Noriyuki Suzuki1, Koyo Takimoto1, Nobuyuki Kawashima1
1Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Introduction:
Cathepsin K is highly expressed in osteoclasts and plays an essential role in bone resorption. NC-2300 is an artificially designed cathepsin K inhibitor, and its application to experimentally induced arthritis induces down-regulation of bone destruction. In this study, we evaluated the effects of NC-2300 on inflammation and bone destruction in experimentally induced rat periapical lesions.
Methods:
The dental pulps of lower first molars in rats were extirpated, and the pulp chambers were left open to the oral environment. NC-2300 and phosphate-buffered saline were administered orally twice a day in the experimental and control groups, respectively. Animals were sacrificed on day 21, and the mandibles were extracted. The left hemimandibles were used for micro-computed tomographic and histologic examination. For the right hemimandibles, RNA was extracted from the periapical tissues surrounding the root apices, and inflammatory mediator expression was examined by real-time polymerase chain reaction using complementary DNA converted from extracted RNA.
Results:
The size of the periapical lesion, number of tartrate-resistant acid phosphatase-positive osteoclasts and major histocompatibility complex class II molecule-expressing macrophages in the experimental group decreased significantly when compared with the control group. The expression of proinflammatory cytokines in the experimental group was significantly suppressed when compared with the control group.
Conclusions:
These results suggest that the cathepsin K inhibitor may inhibit not only cathepsin K activity in osteoclasts but also inflammatory mediator synthesis relating to osteoclastogenesis, and these synergistic effects may be involved in the suppression of periapical lesion expansion.
Insights
NC-2300, a cathepsin K inhibitor, reduced inflammation and bone destruction in rat periapical lesions. This suggests potential for treating inflammatory bone loss by targeting osteoclast activity and inflammatory mediators.
Area of Science:
- Oral Biology
- Immunology
- Pharmacology
Background:
- Cathepsin K is crucial for osteoclast-mediated bone resorption.
- NC-2300 is a novel cathepsin K inhibitor with demonstrated efficacy in arthritis models.
- Periapical lesions involve inflammation and bone destruction, necessitating therapeutic interventions.
Purpose of the Study:
- To investigate the therapeutic potential of NC-2300 in experimentally induced rat periapical lesions.
- To evaluate the effects of NC-2300 on both inflammation and bone destruction in this model.
Main Methods:
- Periapical lesions were induced in rats by pulp exposure.
- NC-2300 was administered orally to the experimental group, while the control group received a placebo.
- Micro-computed tomography, histology, and real-time PCR were used to assess lesion size, osteoclast activity, macrophage infiltration, and inflammatory mediator expression.
Main Results:
- NC-2300 significantly reduced periapical lesion size and the number of osteoclasts and macrophages.
- Expression of pro-inflammatory cytokines was significantly suppressed in the NC-2300 treated group.
- Histological analysis confirmed reduced bone destruction in the experimental group.
Conclusions:
- NC-2300 effectively inhibits inflammation and bone destruction in experimental periapical lesions.
- The dual action of inhibiting osteoclast activity and inflammatory mediator synthesis contributes to lesion suppression.
- NC-2300 shows promise as a therapeutic agent for conditions involving inflammatory bone loss.
