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PPP1R3A抑制钙化性肌腱病中的骨生成并负向调节细胞内钙水平。

PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy.

作者信息

Hu Chao, Ma Lin, Gao Shang, Yang Ming-Yu, Mu Mi-Duo, Chang Le, Huang Pan, Ye Xiao, Wang Wei, Tao Xu, Zhou Bing-Hua, Chen Wan, Tang Kang-Lai

机构信息

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China.

Department of Orthopedics, 904 Hospital of PLA, Wuxi 214000 Jiangsu, China.

出版信息

iScience. 2023 Aug 30;26(10):107784. doi: 10.1016/j.isci.2023.107784. eCollection 2023 Oct 20.

DOI:10.1016/j.isci.2023.107784
PMID:37876608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10590817/
Abstract

Calcific tendinopathy (CT) is defined by the progressive accumulation of calcium crystals in tendonic regions that results in severe pain in patients. The etiology of CT is not fully elucidated. In this study, we elucidate the role of PPP1R3A in CT. A significant decrease in PPP1R3A expression was observed in CT patient tissues, which was further confirmed in tissues from a CT-induced rat model. Overexpression of PPP1R3A reduced the expression of osteo/chondrogenic markers OCN and Sox9, improved tendon tissue architecture, and reduced intracellular Ca2+ levels. Overexpression of SERCA2 and knockdown of Piezo1 decreased expression of osteo/chondrogenic markers and intracellular calcium in PPP1R3A-knockdown tendon cells. Lastly, PPP1R3A expression was regulated at the posttranscriptional level by binding of HuR. Collectively, the present study indicates that PPP1R3A plays an important role in regulating calcium homeostasis in tendon cells via Piezo1/SERCA2, rendering it a promising target for therapeutic interventions of CT.

摘要

钙化性肌腱病（CT）的定义是钙晶体在肌腱区域逐渐积累，导致患者出现严重疼痛。CT的病因尚未完全阐明。在本研究中，我们阐明了PPP1R3A在CT中的作用。在CT患者组织中观察到PPP1R3A表达显著降低，这在CT诱导的大鼠模型组织中得到进一步证实。PPP1R3A的过表达降低了骨/软骨生成标志物OCN和Sox9的表达，改善了肌腱组织结构，并降低了细胞内Ca2+水平。SERCA2的过表达和Piezo1的敲低降低了PPP1R3A敲低肌腱细胞中骨/软骨生成标志物的表达和细胞内钙水平。最后，HuR的结合在转录后水平调节PPP1R3A的表达。总体而言，本研究表明PPP1R3A通过Piezo1/SERCA2在调节肌腱细胞钙稳态中起重要作用，使其成为CT治疗干预的一个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/0c4640595dbd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/e4d2b296a1a7/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/b660dcebeee2/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/3e9344f5dc77/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/5bf1c66ef638/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/cc38e0773e9a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/f9460c295e1b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/0c4640595dbd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/e4d2b296a1a7/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/b660dcebeee2/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/3e9344f5dc77/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/5bf1c66ef638/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/cc38e0773e9a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/f9460c295e1b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6266/10590817/0c4640595dbd/gr6.jpg

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Effect of Octacalcium Phosphate Crystals on the Osteogenic Differentiation of Tendon Stem/Progenitor Cells In Vitro.八钙磷酸盐晶体对肌腱干/祖细胞体外成骨分化的影响。
Int J Mol Sci. 2023 Jan 8;24(2):1235. doi: 10.3390/ijms24021235.
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