Man Ying, Fan Chun, Qu Huijuan, Wang Chenxia, Li Shuangshuang, Cao Guizhen
Department of Stomatology, Shengli Oilfield Central Hospital, No. 31, Jinan Road, Dongying, 257034, China.
Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Clin Oral Investig. 2025 Sep 11;29(10):446. doi: 10.1007/s00784-025-06473-4.
Progesterone (PG) and its target, progesterone receptor (PGR), are important regulators in inflammatory diseases. This study aimed to investigate the specific role of PG in periodontitis and to elucidate the underlying mechanisms involving PGR.
Women with periodontitis, including 250 with PG deficiency, 250 with PG supplementation, and 245 controls (normal PG) were enrolled. The distance between the cemento-enamel junction to the alveolar bone crest (CEJ-ABC) and bone mineral density (BMD) were measured by cone beam computed tomography, and the levels of IL-6 and TNF-α in gingival crevicular fluid were measured by ELISA. In vitro, primary human periodontal mesenchymal stem cells (hPDLSCs) were isolated and treated with LPS in combination with PG and/or RU486 (a PGR antagonist). Osteogenic differentiation was assessed by immunofluorescence of Runx2, OCN, and ALP, and by Alizarin red staining. The inflammatory response was assessed by ELISA of IL-6 and TNF-α. Western blot was performed to evaluate the changes in the ERK/JNK/p38-MAPK signalling pathway.
Significantly higher CEJ-ABC and lower BMD were found in some teeth in the PG deficiency group than in the control and PG supplementation groups. The GCF levels of IL-6 and TNF-α were also significantly higher in the PG deficiency group. At the cellular level, PGR was up-regulated by PG in LPS-treated hPDLSCs. PG inhibits the effects of LPS on inducing inflammatory response (IL-6 and TNF-α) and inhibiting osteogenic differentiation (Runx2, OCN, ALP, and mineralised nodules) in hPDLSCs, but RU864 reversed the above effects of PG. Additionally, PG-induced activation of PGR inhibited the ERK/JNK/p38-MAPK signalling pathway in LPS-treated hPDLSCs.
In women with periodontitis, the alveolar bone resorption and inflammation were more pronounced with PG deficiency. In vitro, PG-induced activation of PGR signalling inhibited inflammation and promoted osteogenesis in hPDLSCs. PG supplementation may be a potential strategy to alleviate periodontitis.
孕酮（PG）及其靶点孕酮受体（PGR）是炎症性疾病的重要调节因子。本研究旨在探讨PG在牙周炎中的具体作用，并阐明涉及PGR的潜在机制。
招募患有牙周炎的女性，包括250例PG缺乏者、250例PG补充者和245例对照者（PG正常）。通过锥形束计算机断层扫描测量牙骨质-釉质界至牙槽嵴顶（CEJ-ABC）的距离和骨密度（BMD），并通过酶联免疫吸附测定法测量龈沟液中IL-6和TNF-α的水平。在体外，分离原代人牙周间充质干细胞（hPDLSCs），并用脂多糖（LPS）联合PG和/或RU486（一种PGR拮抗剂）进行处理。通过Runx2、OCN和ALP的免疫荧光以及茜素红染色评估成骨分化。通过ELISA法检测IL-6和TNF-α评估炎症反应。进行蛋白质免疫印迹法以评估ERK/JNK/p38-MAPK信号通路的变化。
PG缺乏组部分牙齿的CEJ-ABC明显高于对照组和PG补充组，BMD则明显低于对照组和PG补充组。PG缺乏组龈沟液中IL-6和TNF-α水平也显著更高。在细胞水平上，PG在LPS处理的hPDLSCs中上调了PGR。PG抑制LPS对hPDLSCs诱导炎症反应（IL-6和TNF-α）和抑制成骨分化（Runx2、OCN、ALP和矿化结节）的作用，但RU864逆转了PG的上述作用。此外，PG诱导的PGR激活抑制了LPS处理的hPDLSCs中的ERK/JNK/p38-MAPK信号通路。
在患有牙周炎的女性中，PG缺乏时牙槽骨吸收和炎症更为明显。在体外，PG诱导的PGR信号激活抑制了hPDLSCs中的炎症并促进了成骨。补充PG可能是缓解牙周炎的一种潜在策略。
