New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.
Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.
Shimizu
Hideo
H
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nakagami
Hironori
H
Morita
Shosuke
S
Tsukamoto
Ikuyo
I
Osako
Mariana Kiomy
MK
Nakagami
Futoshi
F
Shimosato
Takashi
T
Minobe
Noriko
N
Morishita
Ryuichi
R
D015502:Absorptiometry, Photon; D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption / Q000517:prevention & control*; D002478:Cells, Cultured; D017931:DNA Primers; D004285:Dogs; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D010510:Periodontal Diseases / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*
D017931:DNA Primers; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides