Carbon monoxide-releasing molecule suppresses inflammatory and osteoclastogenic cytokines in nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via the heme oxygenase-1 pathway

Song,Ling; Li,Jingyuan; Yuan,Xiao; Liu,Wen; Chen,Zhenggang; Guo,Dawei; Yang,Fang; Guo,Qingyuan; Song,Hui

doi:10.3892/ijmm.2017.3129

Carbon monoxide-releasing molecule suppresses inflammatory and osteoclastogenic cytokines in nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via the heme oxygenase-1 pathway

Authors:
- Ling Song
- Jingyuan Li
- Xiao Yuan
- Wen Liu
- Zhenggang Chen
- Dawei Guo
- Fang Yang
- Qingyuan Guo
- Hui Song
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Affiliations: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Dentistry, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Oral Mucosal Diseases, School of Dentistry, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Stomatology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
Published online on: September 8, 2017 https://doi.org/10.3892/ijmm.2017.3129
Pages: 1591-1601

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Abstract

Smoking is identified as a risk factor for periodontitis. Carbon monoxide (CO)-releasing molecule-3 (CORM-3) is a compound that has demonstrated anti-inflammatory effects in vitro and in vivo studies. The present study aimed to investigate the effects of CORM-3 on the expression of inflammatory and osteoclastogenic cytokines in human periodontal ligament cells (PDLCs) stimulated by nicotine and lipopolysaccharide (LPS). The cells were pretreated with CORM-3 and then cultured in medium in the presence of nicotine and LPS. The mRNA and protein expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX‑2), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and heme oxygenase-1 (HO-1) were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The mRNA and protein expression levels of these cytokines were also evaluated in PDLCs transiently transfected with HO-1 small interfering RNA (siRNA) in response to nicotine and LPS stimulation. CORM-3 attenuated the LPS- and nicotine-induced production of PGE2, COX-2 and RANKL in human PDLCs by releasing CO, and upregulated the expression of OPG. However, these effects of CORM-3 were abrogated when HO-1 siRNA was transiently transfected into the cells. These results demonstrate that CORM-3 exerts anti-inflammatory and anti-osteoclastogenic effects on nicotine- and LPS-stimulated human PDLCs via the HO-1 pathway, which suggests its promising potential for use in the treatment of inflammatory periodontal disease.

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