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
Affiliations
Chao Hu
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Department of Orthopedics, 904 Hospital of PLA, Wuxi 214000 Jiangsu, China
Lin Ma
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Shang Gao
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Ming-Yu Yang
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Mi-Duo Mu
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Le Chang
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Pan Huang
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Xiao Ye
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Wei Wang
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Xu Tao
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Bing-Hua Zhou
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China
Wan Chen
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Corresponding author
Kang-Lai Tang
Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing 400000, China; Corresponding author
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.
