Publisher：Scientific Reports  

Alveolar bone loss caused by periodontal disease eventually leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are the tissue-specific cells for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. Here, we investigated the role of erythropoietin receptor (EPOR), which regulates the microenvironment-modulating function of mesenchymal stem cells, in PDLSC-based periodontal therapy. We isolated PDLSCs from patients with chronic periodontal disease and healthy donors, referred to as PD-PDLSCs and Cont-PDLSCs, respectively. PD-PDLSCs exhibited reduced potency of periodontal tissue regeneration and lower expression of EPOR compared to Cont-PDLSCs. EPOR-silencing suppressed the potency of Cont-PDLSCs mimicking PD-PDLSCs, whereas EPO-mediated EPOR activation rejuvenated the reduced potency of PD-PDLSCs. Furthermore, we locally transplanted EPOR-silenced and EPOR-activated PDLSCs into the gingiva around the teeth of ligament-induced periodontitis model mice and demonstrated that EPOR in PDLSCs participated in the regeneration of the periodontal ligament, cementum, and alveolar bone in the ligated teeth. The EPOR-mediated paracrine function of PDLSCs maintains periodontal immune suppression and bone metabolic balance via osteoclasts and osteoblasts in the periodontitis model mice. Taken together, these results suggest that EPOR signaling is crucial for PDLSC-based periodontal regeneration and paves the way for the development of novel options for periodontal therapy.

DOI： 10.1038/s41598-024-57361-y

Scopus

Language：English  

Alveolar bone loss caused by periodontal disease eventually leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are the tissue-specific cells for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. Here, we investigated the role of erythropoietin receptor (EPOR), which regulates the microenvironment-modulating function of mesenchymal stem cells, in PDLSC-based periodontal therapy. We isolated PDLSCs from patients with chronic periodontal disease and healthy donors, referred to as PD-PDLSCs and Cont-PDLSCs, respectively. PD-PDLSCs exhibited reduced potency of periodontal tissue regeneration and lower expression of EPOR compared to Cont-PDLSCs. EPOR-silencing suppressed the potency of Cont-PDLSCs mimicking PD-PDLSCs, whereas EPO-mediated EPOR activation rejuvenated the reduced potency of PD-PDLSCs. Furthermore, we locally transplanted EPOR-silenced and EPOR-activated PDLSCs into the gingiva around the teeth of ligament-induced periodontitis model mice and demonstrated that EPOR in PDLSCs participated in the regeneration of the periodontal ligament, cementum, and alveolar bone in the ligated teeth. The EPOR-mediated paracrine function of PDLSCs maintains periodontal immune suppression and bone metabolic balance via osteoclasts and osteoblasts in the periodontitis model mice. Taken together, these results suggest that EPOR signaling is crucial for PDLSC-based periodontal regeneration and paves the way for the development of novel options for periodontal therapy.

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：Web   Country：Japan  

【背景と目的】横紋筋肉腫は胎児の中胚葉または間葉組織に由来する悪性腫瘍であり、小児では頻度が高いが、成人での発症は稀である。我々は成人の側頭下窩に発生した横紋筋肉腫を経験したので報告する。【症例】患者は38歳男性で、開口障害と右側オトガイ部・下唇の痺れを自覚され、当院を紹介受診した。初診時、右側顎関節部の腫脹と圧痛、右側オトガイ部・下唇の知覚鈍麻を認め、開口量は25mmであった。パノラマエックス線写真では、右側上顎洞後壁の前方への圧排と、下顎切痕を中心とした軽度の吸収を認めた。造影CTでは側頭下窩に造影性の低い内部不均一な腫瘤様病変を認め、上顎洞後壁の前内方への圧排を伴っていた。PET-CTでは病変中央部に中等度、周辺に弱いFDG集積を認めた。頸部リンパ節転移および遠隔転移は認めなかった。MRIでは病変はT2強調画像にて比較的高い信号を主体とした分葉状で、下顎骨および咬筋への浸潤を認めた。Time intensity curveは漸増型で、不均一な造影性を呈していた。造影CTでは病変の低い造影性、周囲組織の圧排像より、神経原性腫瘍、筋原性腫瘍を疑ったが、MRIでは浸潤傾向を呈し、軟部肉腫の診断となった。生検により、血管が少なく間質の割合が多く、MyoD1変異を有する紡錘細胞型横紋筋肉腫と診断された。【考察】MRIのTime intensity curveが漸増型を呈した点は病理像においての比較的多い間質を反映していると解釈でき、造影CTでの低い造影性は撮影時のタイミングの影響と考えられた。

Language：Japanese  

Language：Japanese