PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy
Summary: 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 express...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223018618 |
| _version_ | 1797647826509889536 |
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| author | Chao Hu Lin Ma Shang Gao Ming-Yu Yang Mi-Duo Mu Le Chang Pan Huang Xiao Ye Wei Wang Xu Tao Bing-Hua Zhou Wan Chen Kang-Lai Tang |
| author_facet | Chao Hu Lin Ma Shang Gao Ming-Yu Yang Mi-Duo Mu Le Chang Pan Huang Xiao Ye Wei Wang Xu Tao Bing-Hua Zhou Wan Chen Kang-Lai Tang |
| author_sort | Chao Hu |
| collection | DOAJ |
| description | Summary: 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 ex vivo 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. |
| first_indexed | 2024-03-11T15:23:11Z |
| format | Article |
| id | doaj.art-7ad0e8df2e2d4f07989ea0d27c58a576 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:23:11Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7ad0e8df2e2d4f07989ea0d27c58a5762023-10-28T05:08:26ZengElsevieriScience2589-00422023-10-012610107784PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathyChao Hu0Lin Ma1Shang Gao2Ming-Yu Yang3Mi-Duo Mu4Le Chang5Pan Huang6Xiao Ye7Wei Wang8Xu Tao9Bing-Hua Zhou10Wan Chen11Kang-Lai Tang12Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Department of Orthopedics, 904 Hospital of PLA, Wuxi 214000 Jiangsu, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, ChinaDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Corresponding authorDepartment of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Corresponding authorSummary: 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 ex vivo 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.http://www.sciencedirect.com/science/article/pii/S2589004223018618OrthopedicsMolecular biologyCell biology |
| spellingShingle | Chao Hu Lin Ma Shang Gao Ming-Yu Yang Mi-Duo Mu Le Chang Pan Huang Xiao Ye Wei Wang Xu Tao Bing-Hua Zhou Wan Chen Kang-Lai Tang PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy iScience Orthopedics Molecular biology Cell biology |
| title | PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| title_full | PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| title_fullStr | PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| title_full_unstemmed | PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| title_short | PPP1R3A inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| title_sort | ppp1r3a inhibits osteogenesis and negatively regulates intracellular calcium levels in calcific tendinopathy |
| topic | Orthopedics Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223018618 |
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