Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase.
Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase.
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DOI：
10.1080/21655979.2021.1928930
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Liu D;Du J;Sun J;Li M
含氮双膦酸盐（BPs）诱导人牙周膜成纤维细胞（HPdLFs）大量产生活性氧（ROS）是导致BPs相关性颌骨骨坏死的主要因素。此外，由ROS诱导的成纤维细胞的氧化应激和凋亡与MAPK的激活密切相关。甲状旁腺相关蛋白（PTHrP）可通过调节MAPK磷酸酶1（MKP 1）的水平来阻断MAPK的活性。推测PTHrP可能通过调节MKP 1的表达水平，抑制含氮BP诱导的HPdLF凋亡。在此，阿仑膦酸钠盐三水合物（含氮BP，FOS）和HPdLF共培养24 h、48 h和72 h，并分别测定ROS和凋亡水平。共培养48 h后，FOS可显著增加细胞内ROS水平和细胞凋亡，p38、ERK 1/2和p66 Shc磷酸化水平升高。而p38和ERK 1/2抑制剂可显著减少HPdLF的凋亡。有趣的是，PTHrP预处理显著降低了p38、ERK 1/2和p66 Shc的磷酸化水平。更重要的是，MKP 1抑制剂血根碱抑制PTHrP引起的p38、ERK 1/2和p66 Shc的去磷酸化水平。总之，PTHrP可以通过激活MKP 1磷酸酶抑制含氮BP诱导的HPdLF凋亡。
Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associated with the activation of MAPK. Parathyroid hormone-related protein (PTHrP) can block the activity of MAPK by regulating the levels of MAPK phosphatase 1 (MKP1). Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Herein, alendronate sodium salt trihydrate (nitrogen-containing BP, FOS) and HPdLFs were co-cultured for 24 h, 48 h, and 72 h, and the levels of ROS and apoptosis were determined, respectively. After 48 h co-culture, FOS significantly increased the levels of ROS and apoptosis, and high phosphorylation levels of p38, ERK1/2 and p66Shc were found in this study. However, the inhibitors of p38 and ERK1/2 significantly reduced the apoptosis of HPdLFs. Interestingly, PTHrP pre-treatment significantly reduced the phosphorylation levels of p38, ERK1/2, and p66Shc. More importantly, MKP1 inhibitor sanguinarine inhibited the dephosphorylation levels of p38, ERK1/2, and p66Shc caused by PTHrP. Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase.
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影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
DOI：
10.1093/gerona/glt079
发表时间：
2013-10-01
影响因子：
5.1
作者：
Almeida, Maria;OBrien, Charles A.
通讯作者：
OBrien, Charles A.
影响因子：
4.5
作者：
Checa J;Aran JM
通讯作者：
Aran JM
影响因子：
5.3
作者：
Kim, AH;Khursigara, G;Chao, MV
通讯作者：
Chao, MV
影响因子：
4.8
作者：
Franklin, CC;Kraft, AS
通讯作者：
Kraft, AS