2. Academic Validation
  3. Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling

Morroniside attenuates apoptosis and pyroptosis of chondrocytes and ameliorates osteoarthritic development by inhibiting NF-κB signaling

  • J Ethnopharmacol. 2021 Feb 10;266:113447. doi: 10.1016/j.jep.2020.113447.
Huan Yu 1,  Sai Yao 1,  Chengchong Zhou 1,  Fangda Fu 1,  Huan Luo 2,  Weibin Du 3,  Hongting Jin 1,  Peijian Tong 1,  Di Chen 4,  Chengliang Wu 5,  Hongfeng Ruan 6
Affiliations

Affiliations

  • 1 Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China; The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
  • 2 Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
  • 3 Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 4 Research Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address: [email protected].
  • 5 Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China; The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China. Electronic address: [email protected].
  • 6 Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China; The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: [email protected].
PMID: 33022338 DOI: 10.1016/j.jep.2020.113447
Abstract

Ethnopharmacological relevance: Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Our previous studies showed that Yougui pills and Bushenhuoxue formula, both TCM prescriptions containing Corni Fructus (CF), have protective effects on osteoarthritis (OA). However, the underlying detailed components in both TCM prescriptions that play therapeutic roles have not been fully defined. Morroniside is a major iridoid glycoside and one of the quality control metrics of CF, but the effects of morroniside on OA remain largely elusive.

Aim of the study: The study aims to assess the therapeutic effects of morroniside on cartilage degeneration using a mouse model of OA.

Material and methods: 8-week-old male C57BL/6J mice were randomly divided into 4 groups: Sham, destabilization of the medial meniscus (DMM)-treated with vehicle, DMM-treated with low dose morroniside and DMM-treated with high dose morroniside. Histological staining, immunostaining, and TUNEL staining were conducted to detect changes in tissue morphology, expression of key molecules in chondrocytes, and chondrocyte Apoptosis, respectively. Osteophyte formation, meniscus calcification, and subchondral sclerosis were quantitated using micro-CT. The expression of chondrocyte markers was also analyzed by Western blot in primary chondrocytes derived from mice treated with morroniside.

Results: Morroniside attenuated the progression of OA in mice, resulting in substantially reduced osteophyte formation and subchondral sclerosis and lower OARSI scores. Specifically, morroniside significantly promoted cartilage matrix synthesis by increasing collagen type II expression and suppressing chondrocyte Pyroptosis. Morroniside administration led to inhibition of matrix metalloproteinase-13 (MMP13), Caspase-1 and nod-like receptor protein-3 (NLRP3) expression in DMM mice and IL-1β-stimulated chondrocytes. In addition, morroniside attenuated the progression of OA by enhancing chondrocyte proliferation and inhibiting chondrocyte Apoptosis. Morroniside also attenuated the progression of OA by inhibiting nuclear factor-κB (NF-κB) signaling.

Conclusion: Morroniside was protective against cartilage matrix degradation and reduced DMM-induced chondrocyte Pyroptosis and Apoptosis by the inhibition of NF-κB signaling.

Keywords

Cartilage degeneration; Morroniside; NF-κB; Osteoarthritis; Pyroptosis.

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