Clinical and Animal Studies of Waist and Knee Scraping Therapy for Knee Osteoarthritis.
Knee osteoarthritis (KOA) is a degenerative condition with knee pain as the main clinical manifestation. Scraping is one of the commonly used traditional Chinese medicine treatment methods, which activates blood circulation, removes blood stasis, reduces inflammation, and so on. Although scholars have proposed that the synergistic treatment of the waist and knee for KOA is superior to simple knee treatment, there is no relevant reference literature on the application of scraping therapy. Therefore, this study aims to explore the effectiveness and potential mechanisms of waist and knee scraping therapy for treating KOA through clinical and animal studies in order to promote its clinical application.
To explore the clinical efficacy of waist and knee scraping therapy in the treatment of KOA from clinical study and increase animal study on this basis to preliminarily explore its mechanism, providing an objective basis for better treatment of KOA.
The clinical study recruited 90 KOA patients and divided them into a control group, a knee scraping group, and a waist and knee scraping group using a random number table method. All patients were evaluated for clinical efficacy, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Score. The KOA rat model was established using the Hulth method. The rats were randomly divided into a control group, KOA group, waist scraping group, knee scraping group, and waist and knee scraping group. During the intervention process of rats, the pain sensitivity threshold was measured, and HE staining was performed on the synovium and cartilage. The protein and mRNA expression levels of TNF-α, IL- 1β, IL-6, PGP9.5, SP and TRPA1, TRPV4, SP, and NGF were measured by Western blot and real-time PCR.
In the clinical study, the clinical efficacy of the 2 scraping groups was significantly higher than that of the control group. The clinical efficacy of the waist and knee scraping group on the 60th day of treatment was significantly higher than that of the knee scraping group. In terms of improving WOMAC scores, all 3 groups had significance; The function and total score of the waist and knee scraping group on the 28th day of treatment, as well as the pain, function, and total score on the 60th day, were lower than those of the knee scraping group. In terms of improving pain while standing, pain when walking on flat ground, and total score, the scraping group had significant differences. The score of heavy limbs in the waist and knee scraping group was lower than that in the knee scraping group. In an animal study, during the 4th week after modeling, there were differences in the pain sensitivity threshold between the KOA group and the waist scraping group compared to the control group, while there were differences in the pain sensitivity threshold between the knee scraping group and the waist and knee scraping group compared to the KOA group. The expression levels of various proteins and genes in the KOA group and waist scraping group increased compared to the control group; The knee scraping group and the waist and knee scraping group were lower than those in the KOA group.
Scraping therapy can significantly alleviate knee joint pain and stiffness, improve joint function, and improve clinical efficacy, and the short-term and long-term effects of waist and knee scraping therapy are more significant. The scraping therapy has a definite therapeutic effect on KOA rats, which can improve the threshold of cold hyperalgesia and mechanical hyperalgesia, and the waist and knee scraping therapy is more obvious. This may be related to reducing inflammatory reactions in synovial and ganglion tissues.
Jin Q
,Chen M
,Kong J
,Chen D
,Wu X
,Shi X
,Jie L
,Yu L
,Li S
,Dai Z
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Identification of lncRNA and mRNA Biomarkers in Osteoarthritic Degenerative Meniscus by Weighted Gene Coexpression Network and Competing Endogenous RNA Network Analysis.
Long noncoding RNAs (lncRNAs) play a crucial role in varieties of biological processes. This study is aimed at investigating meniscal degeneration-specific lncRNAs and mRNAs and their related networks in knee osteoarthritis (KOA).
The dataset GSE98918, which included 24 meniscus samples and related clinical data, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the meniscus between KOA and control groups were identified. Based on the enriched differentially expressed lncRNAs and mRNAs, we constructed the coexpression network using WGCNA (weighted correlation network analysis) and identified the critical module related to KOA. For mRNAs in the key module, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out using the DAVID database. A competing endogenous RNA network (ceRNA) based on the screened mRNAs, lncRNAs, and related miRNAs was constructed to reveal presumptive biomarkers further. Finally, the hub lncRNAs and mRNAs were screened, and the diagnostic value was evaluated using a receiver operating characteristic (ROC) curve. Hub mRNAs were validated using the dataset GSE113825.
We screened 208 significantly differentially expressed lncRNAs and mRNAs in menisci between the KOA and non-KOA samples, which were enriched in sixteen modules using WGCNA, especially the green module. Coexpression network based on the enriched differentially expressed lncRNAs and mRNAs in the green module uncovered 5 lncRNAs and 56 mRNAs. The lncRNA-miRNA-mRNA ceRNA network revealed that lnc-HLA-DQA1-5, lnc-RP11-127H5.1.1-1, lnc-RTN2-1, IGFBP4 (insulin-like growth factor binding protein 4), and KLF2 (Kruppel-like factor 2) were significantly correlated with the meniscus degeneration of KOA. ROC curve analysis revealed that these hub lncRNAs and mRNAs showed excellent diagnostic value for KOA.
These hub lncRNAs and mRNAs were potential prognostic biomarkers for the meniscus degeneration of KOA. Further studies are required to validate these new biomarkers and better understand the pathological process of the meniscus degeneration of KOA.
Zhao J
,Su Y
,Jiao J
,Wang Z
,Fang X
,He X
,Zhang X
,Liu Z
,Xu X
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Prediction of MicroRNA and Gene Target in Synovium-Associated Pain of Knee Osteoarthritis Based on Canonical Correlation Analysis.
Inflammation plays a central role in knee osteoarthritis (OA) pathogenesis (C. R. Scanzello, 2017). The synovial membrane inflammation is associated with disease progression and represents a primary source of agony in knee OA (L. A. Stoppiello et al., 2014). Many inflammatory mediators may have biomarker utility. To identify synovium related to knee OA pain biomarkers, we used canonical correlation analysis to analyze the miRNA-mRNA dual expression profiling data and extracted the miRNAs and mRNAs. After identifying miRNAs and mRNAs, we built an interaction network by integrating miRWalk2.0. Then, we extended the network by increasing miRNA-mRNA pairs and identified five miRNAs and four genes (TGFBR2, DST, TBXAS1, and FHLI) through the Spearman rank correlation test. For miRNAs involved in the network, we further performed the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses, whereafter only those mRNAs overlapped with the Online Mendelian Inheritance in Man (OMIM) genetic database were analyzed. Receiver operating characteristic (ROC) curve and support vector machine (SVM) classification were taken into the analysis. The results demonstrated that all the recognized miRNAs and their gene targets in the network might be potential biomarkers for synovial-associated pain in knee OA. This study predicts the underlying risk biomarkers of synovium pain in knee OA.
Wang H
,Hu Y
,Xie Y
,Wang L
,Wang J
,Lei L
,Huang M
,Zhang C
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Mechanism of drug-pairs Astragalus Mongholicus-Largehead Atractylodes on treating knee osteoarthritis investigated by GEO gene chip with network pharmacology and molecular docking.
Investigations into the therapeutic potential of Astragalus Mongholicus (AM, huáng qí) and Largehead Atractylodes (LA, bái zhú) reveal significant efficacy in mitigating the onset and progression of knee osteoarthritis (KOA), albeit with an elusive mechanistic understanding. This study delineates the primary bioactive constituents and their molecular targets within the AM-LA synergy by harnessing the comprehensive Traditional Chinese Medicine (TCM) network databases, including TCMSP, TCMID, and ETCM. Furthermore, an analysis of 3 gene expression datasets, sourced from the gene expression omnibus database, facilitated the identification of differential genes associated with KOA. Integrating these findings with data from 5 predominant databases yielded a refined list of KOA-associated targets, which were subsequently aligned with the gene signatures corresponding to AM and LA treatment. Through this alignment, specific molecular targets pertinent to the AM-LA therapeutic axis were elucidated. The construction of a protein-protein interaction network, leveraging the shared genetic markers between KOA pathology and AM-LA intervention, enabled the identification of pivotal molecular targets via the topological analysis facilitated by CytoNCA plugins. Subsequent GO and KEGG enrichment analyses fostered the development of a holistic herbal-ingredient-target network and a core target-signal pathway network. Molecular docking techniques were employed to validate the interaction between 5 central molecular targets and their corresponding active compounds within the AM-LA complex. Our findings suggest that the AM-LA combination modulates key biological processes, including cellular activity, reactive oxygen species modification, metabolic regulation, and the activation of systemic immunity. By either augmenting or attenuating crucial signaling pathways, such as MAPK, calcium, and PI3K/AKT pathways, the AM-LA dyad orchestrates a comprehensive regulatory effect on immune-inflammatory responses, cellular proliferation, differentiation, apoptosis, and antioxidant defenses, offering a novel therapeutic avenue for KOA management. This study, underpinned by gene expression omnibus gene chip analyses and network pharmacology, advances our understanding of the molecular underpinnings governing the inhibitory effects of AM and LA on KOA progression, laying the groundwork for future explorations into the active components and mechanistic pathways of TCM in KOA treatment.
Wang H
,Zhao X
,Wu Z
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