咬合力のアンロードは歯周炎における歯槽骨の減少を悪化させる

Unloading of occlusal force aggravates alveolar bone loss in periodontitis.

抄録

背景と目的:

歯周炎（PD）は、細菌によって引き起こされる慢性感染性炎症性疾患であり、咬合性外傷を含むいくつかの局所的な要因に関連している。これまでの研究で、外傷性咬合力はPD中の歯槽骨喪失を悪化させる可能性があることが分かっている。しかし、PD中の咬合力低減の効果については不明である。本研究では、PDの発症・進行に及ぼす咬合力低下の影響とそのメカニズムを明らかにし、臨床において歯列欠損を有するPD患者に対する修復提案を行うことを目的とした。また、咬合力アンローディングがPDの新たな局所的要因である可能性も示唆された。

BACKGROUND AND OBJECTIVE: Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD.

材料と方法:

C57BL/6マウスを用い、下顎左側第一大臼歯周囲に5-0シルクを結紮したPDモデル（PD群）および左上顎第一大臼歯を抜歯したアンローディング実験モデル（EX群）を作製した。in vivoでの検証にはTHP-1由来マクロファージを用いた。

MATERIALS AND METHODS: C57BL/6 mice were used to establish a PD model by the ligation of 5-0 silk around the mandibular left first molar (PD group) and an unloading experiment model by the extraction of their left maxillary first molar (EX group). The THP-1-derived macrophages were used to verify in vivo results.

結果:

RESULTS: Micro-CT scanning and H&E staining results consistently showed that PD + EX group experienced the most severe alveolar bone resorption as compared to PD group and control group. Further RNA-sequencing analysis suggested that occlusal force unloading significantly enhanced osteoclastic resorption, inhibited osteoblastic activity, and promotes M1 and M2 macrophages polarization. Immunofluorescence staining (IF) results showed that compared with the PD group, PD + EX group significantly increased the ratio of M1/M2 polarization. Similar results were observed by RT-qPCR and IF in vitro: removal of compressive force led to an increased ratio of M1/M2 polarization in LPS-stimulated THP-1-derived macrophages.

結論:

本研究は、咬合力負荷解除がPD時のM1/M2マクロファージ分極率を上昇させることにより骨吸収を悪化させることを示し、これまで知られていなかったPDの局所的要因を示唆するとともに、歯科医師が残存歯質の維持のために欠損歯を修復する際の新しい知見を提供するものであった。

CONCLUSIONS: Our study demonstrated that occlusal force unloading aggravates bone resorption by increasing the ratio of M1/M2 macrophages polarization during PD, suggesting a previously unknown local contributing factor for PD, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition.