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AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway |
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| Authors: | Fangda Fu Huan Luo Yu Du Yuying Chen Kun Tian Jin Pan Jian Li Nani Wang Ronghua Bao Hongting Jin Peijian Tong Hongfeng Ruan Chengliang Wu |
| Institution: | 1. Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Writing - original draft (equal);2. Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal);3. The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal);4. The Fourth Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China Contribution: Formal analysis (equal), Software (equal);5. Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal);6. Department of Architecture, School of Architecture, China Academy of Art, Hangzhou, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal);7. Department of Orthopaedics, Hangzhou Ninth People's Hospital, Hangzhou, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal);8. Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China;9. Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, China;10. Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal);11. Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China;12. Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China Contribution: Formal analysis (equal), Methodology (equal), Software (equal), Writing - original draft (equal), Writing - review & editing (equal) |
| Abstract: | Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1β. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP. |
| Keywords: | Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex herb pair diabetes Nrf2/Keap1 signalling osteoporosis pyroptosis |