Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice

Abstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis...

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Main Authors: Zhen Li, Zhenyue Chen, Jiayi Chen, Zhutong Liu, Zehui Li, He Sun, Xiaochao Wang, Jinqiang Wei, Xuewei Cao, Decai Zheng
Format: Article
Language:English
Published: BMC 2023-04-01
Series:Chinese Medicine
Subjects:
Online Access:https://doi.org/10.1186/s13020-023-00748-2
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author Zhen Li
Zhenyue Chen
Jiayi Chen
Zhutong Liu
Zehui Li
He Sun
Xiaochao Wang
Jinqiang Wei
Xuewei Cao
Decai Zheng
author_facet Zhen Li
Zhenyue Chen
Jiayi Chen
Zhutong Liu
Zehui Li
He Sun
Xiaochao Wang
Jinqiang Wei
Xuewei Cao
Decai Zheng
author_sort Zhen Li
collection DOAJ
description Abstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis F.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms. Materials and methods Murine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1β for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 μM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 μM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated. Results MON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1β-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores. Conclusions MON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.
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spelling doaj.art-a09ad9f558d549f295fcf18220e6f8a42023-04-23T11:28:05ZengBMCChinese Medicine1749-85462023-04-0118111610.1186/s13020-023-00748-2Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in miceZhen Li0Zhenyue Chen1Jiayi Chen2Zhutong Liu3Zehui Li4He Sun5Xiaochao Wang6Jinqiang Wei7Xuewei Cao8Decai Zheng9The Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe First Clinical College of Guangzhou, University of Chinese MedicineZhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineThe Second Clinical College of Guangzhou, University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese MedicineAbstract Background Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis F.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms. Materials and methods Murine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1β for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 μM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 μM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated. Results MON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1β-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores. Conclusions MON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.https://doi.org/10.1186/s13020-023-00748-2MonotropeinOsteoarthritisCartilage matrix degradationApoptosisPyroptosis
spellingShingle Zhen Li
Zhenyue Chen
Jiayi Chen
Zhutong Liu
Zehui Li
He Sun
Xiaochao Wang
Jinqiang Wei
Xuewei Cao
Decai Zheng
Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
Chinese Medicine
Monotropein
Osteoarthritis
Cartilage matrix degradation
Apoptosis
Pyroptosis
title Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
title_full Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
title_fullStr Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
title_full_unstemmed Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
title_short Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
title_sort monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice
topic Monotropein
Osteoarthritis
Cartilage matrix degradation
Apoptosis
Pyroptosis
url https://doi.org/10.1186/s13020-023-00748-2
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