Duhuo Jisheng Decoction in reduction of inflammatory response via Transforming growth factor-β/Smad signaling pathway for repairing rabbit articular cartilage Injury: A Randomized Controlled Trial

Chao Ye; Zheng Yang; Pengyang Li; Yingdong Lu; Tiancheng Lyu; Yuxuan Liu; Xinmiao Zhou; Pengyuan Zhao; Jing Chen

doi:10.1016/j.intimp.2024.113646

Duhuo Jisheng Decoction in reduction of inflammatory response via Transforming growth factor-β/Smad signaling pathway for repairing rabbit articular cartilage Injury: A Randomized Controlled Trial

Int Immunopharmacol. 2024 Nov 24:144:113646. doi: 10.1016/j.intimp.2024.113646. Online ahead of print.

Authors

Chao Ye¹, Zheng Yang², Pengyang Li¹, Yingdong Lu³, Tiancheng Lyu¹, Yuxuan Liu¹, Xinmiao Zhou⁴, Pengyuan Zhao¹, Jing Chen⁵

Affiliations

¹ Orthopedics Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, PR China.
² School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, PR China.
³ Pathology department, Guang'anmen Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing 100053, PR China.
⁴ Orthopedics Department, Huguosi Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100032, PR China.
⁵ Preventive Treatment of Disease Department, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, PR China. Electronic address: jchen@bucm.edu.cn.

PMID: 39586228
DOI: 10.1016/j.intimp.2024.113646

Abstract

Objective: This study aims to investigate the mechanism underlying the effect of Duhuo Jisheng Decoction on the repair of rabbit articular cartilage injury through a reduction in the inflammatory response mediated by the Transforming growth factor (TGF)-β/Smad signaling pathway.

Methods: A rabbit articular cartilage injury model was constructed using a ring bone extraction drill. Twenty-four Japanese white rabbits were randomly divided into six groups, namely Sham operation, model, low-dose Duhuo Jisheng Decoction, medium-dose Duhuo Jisheng Decoction, high-dose Duhuo Jisheng Decoction, and positive control groups. The treatment lasted 12 weeks. Gross observation, International Cartilage Repair Society score, Wakitani score, and Micro-computed tomography analysis were used to evaluate the structural repair of cartilage injury. Histology and immunohistochemistry were used to observe the proteoglycan, P-TβRII, P-Smad2, and type II collagen expression levels. Enzyme-linked immunosorbent assay was used to analyze the concentrations of Matrix Metalloproteinase-13 and Syndecan-4 in the joint fluid; and RT-PCR and Western Blot were used to observe the mRNA and protein expressions of ALK5, Sox-9, P-Smad3, and TGF-β1 at the injury repair site.

Results: The repair effect of cartilage injury, as seen through gross observation and quantitative scoring, was better in all the Duhuo Jisheng Decoction treatment groups than in the model group. The medium dose group of Duhuo Jisheng Decoction had the best repair effect. We observed remarkable structural restoration of cartilage injury in the medium-dose Duhuo Jisheng Decoction group, with the subchondral bone presenting a distinct hierarchy, and parameters such as bone volume fraction and trabecular separation/spacing being significantly augmented. We found high expression levels of proteoglycans, P-TβRII, P-Smad2, and type II collagen. The concentrations of Matrix Metalloproteinase-13 and Syndecan-4 in the joint fluid were significantly lower following treatment. The low gene expression levels of ALK5, Sox-9, P-Smad3, and TGF-β1 in the injury site of the model group could be reversed in the medium-dose Duhuo Jisheng Decoction group.

Conclusion: Duhuo Jisheng Decoction can repair rabbit cartilage injury and reverse the levels of inflammatory factors in the joint fluid. The mechanism underlying its therapeutic effect is related to the activation of the TGF-β/Smad signaling pathway. This study provides a reliable basis for using Duhuo Jisheng Decoction to treat cartilage injury following knee osteoarthritis.

Keywords: Articular Cartilage Injury; Duhuo Jisheng Decoction; Inflammatory Response; Knee Osteoarthritis; Transforming growth factor-β/Smad Signaling Pathway.