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Lingzhi and San-Miao-San with hyaluronic acid gel mitigate cartilage degeneration in anterior cruciate ligament transection induced osteoarthritis.

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机构: [a]Faulty of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, China [b]Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, China [c]Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China [d]Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China [e]Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China [f]Department of Traumatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China [g]The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, China [h]The Joint Center for Infection and Immunity, Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China [i]Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong [j]Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, China
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关键词: Articular cartilage Hyaluronic acid gel Lingzhi and San-Miao-San Osteoarthritis Subchondral trabecular bone

摘要:
To investigate the mitigate efficacy of Chinese medicine Lingzhi (LZ) and San-Miao-San (SMS) combined with hyaluronic acid (HA)-gel in attenuating cartilage degeneration in traumatic osteoarthritis (OA). The standardized surgery of anterior cruciate ligament transection (ACLT) was made from the medial compartment of right hind limbs of 8-week-old female SD rats and resulted in a traumatic OA. Rats (n ​= ​5/group) were treated once intra-articular injection of 50 ​μl HA-gel, 50 ​μl HA-gel+50 ​μg LZ-SMS, 50 ​μl of saline+50 ​μg LZ-SMS and null (ACLT group) respectively, except sham group. Limbs were harvested for μCT scan and histopathological staining 3-month post-treatment. Inflammatory cytokines from plasma and synovial fluid were detected using Immunology Multiplex Assay kit. The putative targets of active compounds in LZ-SMS and known therapeutic targets for OA were combined to construct protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was adopted to predict the potential targets and signaling pathway of LZ-SMS in OA through the tool of DAVID Bioinformatics. In vivo, HA-gel ​+ ​LZ-SMS treatment resulted in a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (total volume of cartilage), compared to ACLT and HA-gel groups. In addition, histological results showed the elevated cartilage matrix, chondrogenic and osteoblastic signals in HA-gel ​+ ​LZ-SMS treatment. Treatment also significantly altered subchondral bone (SCB) structure including an increase in BV/TV, Tb.Th, BMD, Conn.Dn, Tb.N, and DA, as well as a significant decrease in Tb.Sp and Po(tot), which implied a protective effect on maintaining the stabilization of tibial SCB microstructure. Furthermore, there was also a down-regulated inflammatory cytokines and upregulated anti-inflammatory cytokine IL-10 in HA+LZ-SMS group. Finally, 64 shared targets from 37 active compounds in LZ-SMS related to the core genes for the development of OA. LZ-SMS has a putative role in regulating inflammatory circumstance through influencing the MAPK signaling pathway. Our study elucidated a protective effect of HA-gel ​+ ​LZ-SMS in mitigating cartilage degradation and putative interaction with targets and signaling pathway for the development of traumatic OA. Our results provide a biological rationale for the use of LZ-SMS as a potential candidate for OA treatment. © 2020 The Author(s).

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 2 区 骨科
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 骨科
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第一作者机构: [a]Faulty of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, China
通讯作者:
通讯机构: [b]Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, China [e]Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China [f]Department of Traumatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China [g]The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, China [h]The Joint Center for Infection and Immunity, Institute Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China [i]Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong [*a]No. 804, Shengli street, Department of Traumatology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China [*b]No.9 Jinsui Road, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510623, China [*c]Room 904, Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong.
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