Kase Yoshitaka, Morikawa Satoru, Okano Yuji, Hosoi Tatsuya, Yasui Takazumi, Taki-Miyashita Yoko, Yakabe Mitsutaka, Goto Maraku, Ishihara Kazuyuki, Ogawa Sumito, Nakagawa Taneaki, Okano Hideyuki
Regenerative Medicine Research Center, Keio University, 3-25-10 Tonomachi, Kawasaki-Ku, Kawasaki-Shi, 210-0821, Japan.
Division of CNS Regeneration and Drug Discovery, International Center for Brain Science (ICBS), Fujita Health University, 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake-Shi, Aichi, 470-1192, Japan.
Inflamm Regen. 2025 Feb 3;45(1):3. doi: 10.1186/s41232-025-00366-5.
The incidence of periodontitis is high in older individuals. However, its impact on multi-organ frailty remains unclear. We developed mouse models with varying severity and duration of periodontitis to examine its effects.
We generated mouse models with mild and severe periodontitis, categorizing the disease duration into 3-month and 5-month periods for analysis. The organs assessed for frailty included the gastrocnemius muscle, soleus muscle, brain, and femur.
Our study found that periodontitis induced systemic inflammation resembling inflammaging and other symptoms characteristic of age-induced frailty. Notably, muscle impairment developed specifically in slow-twitch muscles, and the femur emerged as the most vulnerable bone, exhibiting reduced bone mineral density even with mild and short-duration periodontitis. This condition resulted in the co-occurrence of bone fragility and slow-twitch muscle dysfunction. Cognitive function assessment revealed increased activated microglia and decreased adult neurogenesis in the hippocampus, impairing spatial learning. Thus, periodontitis induced both physical and cognitive frailties. Therapeutic intervention for the periodontitis, which halted the exacerbation of bone resorption markers, did not restore femur bone mineral density.
This study underscores the role of periodontitis in inducing multifaceted organ frailty with vulnerability, varying by organ, and the necessity of early intervention, particularly regarding bone density loss.
牙周炎在老年人中的发病率很高。然而，其对多器官衰弱的影响仍不清楚。我们建立了具有不同严重程度和持续时间的牙周炎小鼠模型，以研究其影响。
我们生成了轻度和重度牙周炎小鼠模型，将疾病持续时间分为3个月和5个月进行分析。评估衰弱的器官包括腓肠肌、比目鱼肌、大脑和股骨。
我们的研究发现，牙周炎会引发类似于炎症衰老的全身炎症以及其他与年龄相关的衰弱特征症状。值得注意的是，肌肉损伤 specifically 在慢肌中出现，股骨成为最脆弱的骨骼，即使是轻度和短期的牙周炎也会导致骨密度降低。这种情况导致了骨脆性和慢肌功能障碍的共同出现。认知功能评估显示，海马体中活化的小胶质细胞增加，成年神经发生减少，损害了空间学习能力。因此，牙周炎会导致身体和认知方面的衰弱。对牙周炎的治疗干预虽然阻止了骨吸收标志物的恶化，但并未恢复股骨骨密度。
本研究强调了牙周炎在导致多方面器官衰弱中的作用，不同器官的脆弱性各不相同，以及早期干预的必要性，特别是在骨密度损失方面。
