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好中球の存在は歯周組織にRANKLの発現を引き起こし、破骨細胞の形成をもたらす。
The presence of neutrophils causes RANKL expression in periodontal tissue, giving rise to osteoclast formation.
PMID: 32583887 DOI: 10.1111/jre.12779.
抄録
背景と目的:
好中球浸潤および破骨細胞形成の増加は、歯周炎の重要な特徴である。これらの好中球が歯周炎における破骨細胞形成に及ぼす影響は明らかにされていない。そこで、好中球欠損マウスの歯周炎モデルにおいて、好中球が破骨細胞形成に及ぼす影響を検討した。
BACKGROUNDS AND OBJECTIVE: Increased neutrophil infiltration and osteoclast formation are key characteristics of periodontitis. The effect of these neutrophils on osteoclast formation in periodontitis remains unclear. Therefore, we investigated the effects of neutrophils on osteoclast formation in a neutrophil-deficient mouse model of periodontitis.
方法:
METHODS: Anti-Ly6G antibody (Ab) was used for neutrophil depletion in two mouse models: periodontitis and air pouch. In the periodontitis experiments, mice were divided into PBS-administered control (C), control Ab-administered periodontitis (P), and anti-Ly6G Ab-administered periodontitis (P + Ly6G) groups. Periodontitis was induced by ligature of mandibular first molars. In the air pouch experiments, mice were divided into PBS-administered (C), LPS and control Ab-administered (LPS), and LPS and anti-Ly6G Ab-administered (LPS + Ly6G) groups. Neutrophil migration into air pouches was induced by LPS injection. Flow cytometry was used to examine CD11b Ly6G neutrophils in the blood of periodontitis mice and CD11b Ly6G RANKL neutrophils in exudates of air pouch mice. In periodontal tissue, Ly6G neutrophil and RANKL cell numbers in periodontal ligament and alveolar bone areas were estimated using immunohistochemistry, osteoclast numbers were measured using TRAP assay, and alveolar bone loss was determined by H&E staining.
結果:
血液中のCD11b Ly6G好中球の割合は、3日目と7日目にP群の方がC群よりも多かった。しかし、好中球の割合は、P"Zs_A0"+"Zs_A0"Ly6G群の方がC群、P群よりも少なかった。歯周組織では、3日目にP"Zs_A0"+"Zs_A0"Ly6G群の方がP群よりもLy6G好中球数とRANKL細胞数が少なかった。Ly6G好中球数は7日目のP"Zs_A0"+"Zs_A0"Ly6G群ではP群よりも減少したが、RANKL細胞数はP"Zs_A0"+"Zs_A0"Ly6G群では減少しなかった。滲出液では、CD11b Ly6G RANKL好中球数は、C群およびLPS"Zs_A0"+"Zs_A0"Ly6G群よりもLPS群の方が多かった。3日目と7日目の歯周組織における破骨細胞数と歯槽骨減少量は、P群とP"Zs_A0"+"Zs_A0"Ly6G群の方がC群よりも多かった。興味深いことに、3日目の破骨細胞の数はP群よりもP"Zs_A0"+"Zs_A0"Ly6G群の方が少なかった。
RESULTS: In blood, CD11b Ly6G neutrophils were found in greater percentage in the P group than in the C group on days 3 and 7. However, the percentage of neutrophils was lower in the P + Ly6G group than in the C and P groups. In periodontal tissue, the numbers of Ly6G neutrophils and RANKL cells were lower in the P + Ly6G group than in the P group on day 3. Ly6G neutrophil numbers decreased more in the P + Ly6G group than in the P group on day 7, but RANKL cell numbers did not decrease in the P + Ly6G group. In exudates, the number of CD11b Ly6G RANKL neutrophils was greater in the LPS group than in the C and LPS + Ly6G groups. On days 3 and 7, the numbers of osteoclasts and alveolar bone loss were greater in periodontal tissue in the P and P + Ly6G groups than in the C group. Interestingly, there were fewer osteoclasts in the P + Ly6G group than in the P group on day 3.
結論:
好中球欠損は、歯周炎誘発組織において、3日目にのみRANKL細胞と破骨細胞の両方の数の減少を引き起こした。さらに、LPSを注入したエアパウチモデルでは、好中球欠損はRANKL好中球の流入を減少させた。これらの知見は、好中球の存在がRANKLの発現を誘導し、歯周炎の初期段階で破骨細胞の形成を誘導しうることを示唆している。
CONCLUSION: Neutrophil deficiency caused a reduction in numbers of both RANKL cells and osteoclasts in periodontitis-induced tissues only on day 3. Furthermore, in the LPS-injected air pouch model, neutrophil deficiency reduced the influx of RANKL neutrophils. These findings suggest that the presence of neutrophils induces RANKL expression and could induce osteoclast formation in the early stages of periodontitis.
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.