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TMF通过介导FOXO3a/BMPER信号通路抑制骨关节炎软骨中软骨细胞的肥大。

TMF suppresses chondrocyte hypertrophy in osteoarthritic cartilage by mediating the FOXO3a/BMPER pathway.

作者信息

Huang Jishang, Ren Qun, Jiao Linhui, Niu Shuo, Liu Chenghong, Zhou Juan, Wu Longhuo, Yang Yadong

机构信息

Department of Orthopedics, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

College of Pharmacy, Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

出版信息

Exp Ther Med. 2024 May 15;28(1):283. doi: 10.3892/etm.2024.12571. eCollection 2024 Jul.

DOI:10.3892/etm.2024.12571
PMID:38800044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11117099/
Abstract

Osteoarthritis (OA) is a disease of the joints, characterized by chronic inflammation, cartilage destruction and extracellular matrix (ECM) remodeling. Aberrant chondrocyte hypertrophy promotes cartilage destruction and OA development. Collagen X, the biomarker of chondrocyte hypertrophy, is upregulated by runt-related transcription factor 2 (Runx2), which is mediated by the bone morphogenetic protein 4 (BMP4)/Smad1 signaling pathway. BMP binding endothelial regulator (BMPER), a secreted glycoprotein, acts as an agonist of BMP4. 5,7,3',4'-tetramethoxyflavone (TMF) is a natural flavonoid derived from L. Results of our previous study demonstrated that TMF exhibits chondroprotective effects against OA development through the activation of Forkhead box protein O3a (FOXO3a) expression. However, whether TMF suppresses chondrocyte hypertrophy through activation of FOXO3a expression and inhibition of BMPER/BMP4/Smad1 signaling remains unknown. Results of the present study revealed that TMF inhibited collagen X and Runx2 expression, inhibited BMPER/BMP4/Smad1 signaling, and activated FOXO3a expression; thus, protecting against chondrocyte hypertrophy and OA development. However, BMPER overexpression and FOXO3a knockdown impacted the protective effects of TMF. Thus, TMF inhibited chondrocyte hypertrophy in OA cartilage through mediating the FOXO3a/BMPER signaling pathway.

摘要

骨关节炎（OA）是一种关节疾病，其特征为慢性炎症、软骨破坏和细胞外基质（ECM）重塑。异常的软骨细胞肥大促进软骨破坏和OA发展。胶原蛋白X是软骨细胞肥大的生物标志物，由 runt相关转录因子2（Runx2）上调，这是由骨形态发生蛋白4（BMP4）/Smad1信号通路介导的。BMP结合内皮调节因子（BMPER）是一种分泌型糖蛋白，作为BMP4的激动剂。5,7,3',4'-四甲氧基黄酮（TMF）是一种从……中提取的天然黄酮类化合物。我们先前的研究结果表明，TMF通过激活叉头框蛋白O3a（FOXO3a）的表达对OA发展具有软骨保护作用。然而，TMF是否通过激活FOXO3a的表达并抑制BMPER/BMP4/Smad1信号通路来抑制软骨细胞肥大仍不清楚。本研究结果显示，TMF抑制胶原蛋白X和Runx2的表达，抑制BMPER/BMP4/Smad1信号通路，并激活FOXO3a的表达；因此，可预防软骨细胞肥大和OA发展。然而，BMPER的过表达和FOXO3a的敲低影响了TMF的保护作用。因此，TMF通过介导FOXO3a/BMPER信号通路抑制OA软骨中的软骨细胞肥大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/76b17826fee4/etm-28-01-12571-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/40a57da29cff/etm-28-01-12571-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/4b90b2bb20ec/etm-28-01-12571-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/c15cf6b67991/etm-28-01-12571-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/76b17826fee4/etm-28-01-12571-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/40a57da29cff/etm-28-01-12571-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/4b90b2bb20ec/etm-28-01-12571-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/c15cf6b67991/etm-28-01-12571-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01c/11117099/76b17826fee4/etm-28-01-12571-g03.jpg

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