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Cathepsin K Inhibitor Regulates Inflammation and Bone Destruction in Experimentally Induced Rat Periapical Lesions.

Journal of endodontics (2015-05-21)
Noriyuki Suzuki, Koyo Takimoto, Nobuyuki Kawashima

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. 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. 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. 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.

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Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, ≥97% (HPLC)
1-Naphthol, ReagentPlus®, ≥99%
1-Naphthol, BioXtra, ≥99%
1-Naphthol, puriss. p.a., reag. Ph. Eur., ≥99% (GC)
Sulfanilamide, puriss. p.a., ≥99% (calc. to the dried substance)
Sulfanilamide, ≥98%
Tris(tert-butoxy)silanol, 99.999%
Tris(tert-butoxy)silanol, packaged for use in deposition systems
Hematoxylin, certified by the Biological Stain Commission
Nitric oxide, 98.5%