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

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

doi:10.1016/j.isci.2023.107784

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

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

Authors

Chao Hu^{1

2}, Lin Ma¹, Shang Gao¹, Ming-Yu Yang¹, Mi-Duo Mu¹, Le Chang¹, Pan Huang¹, Xiao Ye¹, Wei Wang¹, Xu Tao¹, Bing-Hua Zhou¹, Wan Chen¹, Kang-Lai Tang¹

Affiliations

¹ Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China.
² Department of Orthopedics, 904 Hospital of PLA, Wuxi 214000 Jiangsu, China.

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 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.

Keywords: Cell biology; Molecular biology; Orthopedics.