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标题：Lingzhi and San-Miao-San with hyaluronic acid gel mitigate cartilage degeneration in anterior cruciate ligament transection induced osteoarthritis
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作者：Man Chu ; Ping Wu ; Ming Hong 等
期刊名称：Journal of Orthopaedic Translation
印刷版ISSN：2214-031X
出版年度：2021
卷号：26
页码：132-140
DOI：10.1016/j.jot.2020.07.008
出版社：Elsevier B.V.
摘要：Objective 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). Methods 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. Results 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. Conclusion 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. The translational potential of this article Our results provide a biological rationale for the use of LZ-SMS as a potential candidate for OA treatment.
关键词：Articular cartilage ; Hyaluronic acid gel ; Lingzhi and San-Miao-San ; Osteoarthritis ; Subchondral trabecular bone ; 3D Three-dimensional ; AC Articular cartilage ; Acan Aggrecan ; ACLT Anterior cruciate ligament transection ; BMD Bone mineral density ; BV/TV Bone volume fraction ; CC Calcified cartilage ; Conn.Dn Connectivity density ; DA Degree of anisotropy ; DL Drug-likeness ; ECM Extracellular matrix ; FDR False discovery rate ; GO Gene ontology ; HA Hyaluronic acid ; HC Hyaline cartilage ; KEGG Kyoto Encyclopedia of Genes and Genomes ; LZ-SMS Lingzhi-San-Miao-San ; MZ Middle zone area of articular cartilage ; NC Negative control ; OA Osteoarthritis ; OB Oral bioavailability ; OMIM Online Mendelian Inheritance in Man ; Po(tot) Total porosity ; PPI Protein–protein interaction ; ROI Region of Interest ; SC Superficial cartilage ; SCB Subchondral bone ; Sum Whole cartilage ; SZ Superficial zone of articular cartilage ; Tb.N Trabecular number ; Tb.Pf Trabecular bone pattern factor ; Tb.Sp Trabecular separation ; Tb.Th Trabecular thickness ; TCM Traditional Chinese medicine ; TCMSP Traditional Chinese Medicine Systems Pharmacology Database