Effect of Electro-acupuncture (EA) and Manual Acupuncture (MA) on Markers of Inflammation in knee osteoarthritis

Abstract Background Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both Electro-acupuncture (EA) and Manual Acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA.Methods Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-18, IL-4, IL-10,IL-13,IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CCchemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMasters osteoarthritis index questionnaire (WOMAC) and Visual Analogue Scale (VAS) at baseline and post-treatment.Results Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNFα, IL-1β) and cartilage degradation biomarkers (MMP-3, MMP-13), significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p<0.05). Further, the reduction of TNF-α were more significant in EA when compared to MA (p=0.046). While, there was no significant difference between groups in cytokines IL-1β (p=0.102), MMP-3(p=0.113), MMP-13(p=0.623) or IL-13(p=0.935). Moreover, in both EA and MA the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups.Conclusions 8 weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-α, IL-1β and IL-13.

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Significance of Expression of miR-365, Cartilage Oligomeric Matrix Protein and Inflammatory Factors in Knee Osteoarthritis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2366 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1065-1069

Author(s):

Ren Lin ◽

Jinglai Xue ◽

Junqin Qiu

Keyword(s):

Knee Osteoarthritis ◽

Cartilage Oligomeric Matrix Protein ◽

Matrix Protein ◽

Serum Levels ◽

Inflammatory Factors ◽

Control Group ◽

Observation Group ◽

Logistic Analysis ◽

Tnf Α ◽

And Gender

This study is to investigate the high expression of miR-365, cartilage oligomeric matrix protein (COMP) and inflammatory factors in knee osteoarthritis and their correlation with disease activity. The 94 patients with knee osteoarthritis were selected as the observation group. Controls were 94 healthy people matched according to the age and gender of the observation group. The expression levels of blood miR-365, cartilage oligomeric matrix protein, and the inflammatory IL-6 and TNF-α were compared between two groups and correlations between these indicators and Lysholm knee scores were determined. The serum levels of miR-365, cartilage oligomeric matrix protein and the inflammatory factors IL-6 and TNF-α in osteoarthritis patients exceeded those in the normal control group (P < 0 05), and miR-365 was positively correlated with cartilage oligomeric matrix protein and IL-6 and TNF-α (P < 0 05). In addition, the positive correlation was found between the Lysholm osteoarthritis score and the above factors (P < 0 05). Finally, logistic analysis of elevated peripheral blood miR-365 and COMP is an independent risk factor for osteoarthritis. MiR-365, COMP and inflammatory factors IL-6 and TNF-α are highly expressed in knee osteoarthritis.

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Effectiveness and feasibility of acupuncture for knee osteoarthritis: a pilot randomized controlled trial

Clinical Rehabilitation ◽

10.1177/0269215518790632 ◽

2018 ◽

Vol 32 (12) ◽

pp. 1666-1675 ◽

Cited By ~ 10

Author(s):

Lu-Lu Lin ◽

Yong-Ting Li ◽

Jian-Feng Tu ◽

Jing-Wen Yang ◽

Ning Sun ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Response Rate ◽

Controlled Trial ◽

Womac Pain ◽

Chinese Acupuncture ◽

Randomized Controlled ◽

Acupuncture Intervention ◽

Significant Difference ◽

And Function ◽

Pilot Randomized Controlled Trial

Objective: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. Design: Pilot randomized controlled trial. Setting: Three teaching hospitals in China. Subjects: Patients with knee osteoarthritis (Kellgren grade II or III). Interventions: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. Main measures: The primary outcome was response rate—the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. Results: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. Conclusion: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

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Effect of Moxibustion on the Intestinal Flora of Rats with Knee Osteoarthritis Induced by Monosodium Iodoacetate

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3196427 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yu Chen ◽

Jiuheng Lv ◽

Yejuan Jia ◽

Ruiqing Wang ◽

Zidi Zhang ◽

...

Keyword(s):

Treatment Group ◽

Knee Osteoarthritis ◽

High Throughput Sequencing ◽

Cartilage Damage ◽

Intestinal Flora ◽

Inflammatory Factors ◽

Knee Cartilage ◽

Model Group ◽

Monosodium Iodoacetate ◽

And Cartilage

In this study, a knee osteoarthritis (KOA) rat model induced by monosodium iodoacetate (MIA) was used to study the effect of moxibustion on improving knee cartilage damage and its effect on the intestinal flora. The experimental rats were divided into the normal group (N), model group (M), moxibustion treatment group (MS), and diclofenac sodium treatment group (DS). After 4 weeks, cartilage pathological damage in the knee joint was evaluated using hematoxylin-eosin and safranin O-fast green staining analysis. ELISAs and Western blots were used to detect the expression levels of IL-1β and TNF-α in the serum and cartilage, respectively. The total DNA of the fecal samples was extracted and subjected to high-throughput sequencing of the V3-V4 region of the 16S rRNA gene to analyze the changes in the intestinal flora. In the model group, the cartilage was obviously damaged, the expression levels of IL-1β and TNF-α in the serum and cartilage were increased, and the abundance and diversity of the intestinal flora were decreased. Moxibustion treatment significantly improved the cartilage damage and reduced the concentration of inflammatory factors in the serum and cartilage. The high-throughput sequencing results showed that compared to the model group, the moxibustion treatment regulated some specific species in the intestinal microorganisms rather than the α diversity. In conclusion, our findings suggest that moxibustion treatment may work through two aspects in rats. On one hand, it directly acts on knee cartilage to promote repair, and on the other hand, it regulates the composition of the intestinal flora and reduces the production of inflammatory factors.

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Intra-articular Injection of Culture-Expanded Mesenchymal Stem Cells Without Adjuvant Surgery in Knee Osteoarthritis: A Systematic Review and Meta-analysis

The American Journal of Sports Medicine ◽

10.1177/0363546519892278 ◽

2019 ◽

Vol 48 (11) ◽

pp. 2839-2849 ◽

Cited By ~ 9

Author(s):

Seong Hwan Kim ◽

Yoshi Pratama Djaja ◽

Yong-Beom Park ◽

Jung-Gwan Park ◽

Young-Bong Ko ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Cartilage Repair ◽

Meta Analysis ◽

Risk Of Bias ◽

Mean Difference ◽

Resonance Imaging ◽

Adjuvant Surgery ◽

Significant Difference ◽

Standardized Mean Difference ◽

And Cartilage

Background: Although many clinical studies have assessed the efficacy of mesenchymal stem cells (MSCs) in knee osteoarthritis, evidence on their efficacy remains unclear owing to heterogeneity of cell entity and concomitant procedures. Purpose: To determine the efficacy of culture-expanded MSCs in knee osteoarthritis in terms of clinical outcome and cartilage repair via meta-analysis of randomized controlled trials (RCTs) without adjuvant surgery. Study Design: Meta-analysis. Methods: PubMed, Embase, the Cochrane Library, CINAHL, and Scopus were searched from inception to December 31, 2018. RCTs with culture-expanded MSCs for treating knee osteoarthritis were included. Studies with adjuvant surgery or cell concentrate were excluded. Quality was assessed by the Cochrane Collaboration risk-of-bias tool. For meta-analysis, data on clinical outcomes were measured using a visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); categorization related to improvement was extracted. Results: Six RCTs (203 patients) were included. Two studies were deemed to have a low risk of bias. In pooled analysis, the only significant difference was in the VAS score (mean difference, –13.55; 95% CI, –22.19 to −4.9). In cumulative pain analysis with VAS and WOMAC pain scores, there was significant improvement after treatment (standardized mean difference, –0.54; 95% CI, –0.85 to −0.23). There was no significant difference in cartilage repair assessed by magnetic resonance imaging (standardized mean difference, 0.11; 95% CI, –0.51 to 0.73), WORMS (standardized mean difference, 1.68; 95% CI −14.84 to 18.21), or categorical results (odds ratio, 1.56; 95% CI, 0.32-7.59). Conclusion: Intra-articular injection of culture-expanded MSCs without adjuvant surgery can improve pain for patients experiencing knee osteoarthritis at short-term follow-up (6-12 months). However, evidence regarding function and cartilage repair remains limited.

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Efficacy and Mechanism of Electroacupuncture Treatment of Rabbits With Different Degrees of Knee Osteoarthritis: A Study Based on Synovial Innate Immune Response

Frontiers in Physiology ◽

10.3389/fphys.2021.642178 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anmin Ruan ◽

Qingfu Wang ◽

Yufeng Ma ◽

Dong Zhang ◽

Lili Yang ◽

...

Keyword(s):

Immune Response ◽

Western Blot ◽

Knee Osteoarthritis ◽

Synovial Tissue ◽

Innate Immune Response ◽

Synovial Membrane ◽

Innate Immune ◽

Cartilage Tissue ◽

Inflammatory Factors ◽

And Cartilage

Knee osteoarthritis (KOA) is a chronic degenerative bone and joint disease, which is often clinically manifested as pain, joint swelling, and deformity. Its pathological manifestations are mainly synovial inflammation and cartilage degeneration. This study aims to investigate the efficacy of electro-acupuncture (EA) on model rabbits with varying degrees of KOA and to study the mechanism of EA on KOA based on the innate immune response. Mild and moderate rabbit KOA models were established using a modified Hluth method, and EA was given to both the mild and moderate model groups. The Lequesne-MG index was used to evaluate the behavioral changes in the rabbits before and after EA treatment. Morphological changes in the synovial membrane and cartilage of each group were observed by H&E staining. The Mankin scoring standard and the Krenn scoring standard were used to score the pathology of the cartilage tissue and synovial tissue, respectively. The inflammatory factors and metalloproteinases were detected in the serum of each group by ELISA. The protein and messenger RNA (mRNA) expressions of important elements related to Toll-like receptors (TLRs)-mediated innate immune response in the synovial tissue were detected by Western blot and quantitative PCR (qPCR). The Lequesne-MG index score of the rabbits gradually increased with the modeling prolonged but decreased significantly after EA treatment, indicating that EA has a better effect on alleviating the pain and improving the dysfunction. The morphological analysis showed that the inflammation of and the damage to the synovial membrane and the cartilage tissue gradually deteriorated with the modeling prolonged. However, the synovial membrane inflammation was significantly relieved after EA treatment, and the cartilage injury showed signs of repair. The ELISA analysis showed that, with the modeling prolonged, the serum-related inflammatory factors and mechanism of metalloproteinases gradually increased but decreased after EA treatment. The tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and matrix metalloproteinase3 (MMP3) of EA1 group were significantly lower than those of EA2 group. Both Western blot and qPCR results showed that the protein and mRNA expressions of the elements related to the innate immune response in the synovial membrane increased gradually with the modeling prolonged, but decreased significantly after EA treatment. Additionally, the expression of some components in EA1 group was significantly lower than that in EA2 group. These results confirm that synovial inflammation gradually aggravated with time from the early to mid-stage of KOA. EA alleviated the inflammation and histological changes in KOA rabbits by inhibiting the TLRs-mediated innate synovial immune response. This suggests that using EA in the early stage of KOA may achieve a desirable efficacy.

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A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i6.2177 ◽

2020 ◽

Cited By ~ 1

Author(s):

Masoomeh Yosefifard ◽

Gholamhassan Vaezi ◽

Ali Akbar Malekirad ◽

Fardin Faraji ◽

Vida Hojati

Keyword(s):

Multiple Sclerosis ◽

Interleukin 1 ◽

Serum Levels ◽

Inflammatory Factors ◽

Control Group ◽

Necrosis Factor Alpha ◽

Treatment Groups ◽

Tnf Α ◽

Significant Difference ◽

The Central Nervous System

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS

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Effect of Electro-Acupuncture (EA) and Manual Acupuncture (MA) on Markers of Inflammation in Knee Osteoarthritis

Journal of Pain Research ◽

10.2147/jpr.s256950 ◽

2020 ◽

Vol Volume 13 ◽

pp. 2171-2179

Author(s):

Guang-Xia Shi ◽

Jian-Feng Tu ◽

Tian-Qi Wang ◽

Jing-Wen Yang ◽

Li-Qiong Wang ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Manual Acupuncture ◽

Markers Of Inflammation

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The Effects of Morus alba and Acacia catechu on Quality of Life and Overall Function in Adults with Osteoarthritis of the Knee

Journal of Nutrition and Metabolism ◽

10.1155/2017/4893104 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Douglas S. Kalman ◽

Susan J. Hewlings

Keyword(s):

Cartilage Damage ◽

Type Ii Collagen ◽

Cartilage Degradation ◽

Morus Alba ◽

Osteoarthritis Of The Knee ◽

Significant Difference ◽

Womac Questionnaire ◽

Acacia Catechu ◽

Double Blinded ◽

And Function

The purpose of this study was to determine the effects of UP1306 on discomfort and function in adults with osteoarthritis of the knee. In a randomized, double-blinded, placebo-controlled, parallel design, 135 subjects received UP1306, a standardized, proprietary extract of Morus alba and Acacia catechu, glucosamine chondroitin, or placebo for 12 weeks. Discomfort, stiffness, and activities of daily living measured by the WOMAC questionnaire and VAS (pain/discomfort) were improved within all groups. Range of motion and distance walked were improved. There were no changes in TNFα levels for any of the products. There was a significant difference in urinary C-telopeptides of type II collagen (CTX-II), a marker of cartilage degradation between UP1306, and placebo after 12 weeks (p=0.029). All efficacy measurements were improved from baseline to most time-points for UP1306, the comparator, and placebo without a significant association between the products. There was a significant difference between the changes of uCTX-II for UP1306 and placebo after 12 weeks. Early intervention with UP1306 aimed at reducing bone and cartilage degradation through reported inhibition of catabolic proinflammatory pathways may help to prevent joint cartilage damage. This study is registered with Clinical Trial ID ISRCTN15418623.

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Electroacupuncture versus manual acupuncture for knee osteoarthritis: a randomized controlled pilot trial

Acupuncture in Medicine ◽

10.1177/0964528419900781 ◽

2020 ◽

Vol 38 (5) ◽

pp. 291-300 ◽

Cited By ~ 1

Author(s):

Tian-Qi Wang ◽

Yong-Ting Li ◽

Li-Qiong Wang ◽

Guang-Xia Shi ◽

Jian-Feng Tu ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Statistical Significance ◽

Pilot Trial ◽

Controlled Clinical Trial ◽

Acupuncture Points ◽

Womac Pain ◽

Manual Acupuncture ◽

Current Output ◽

Randomized Controlled ◽

And Function

Objective: We aimed to explore the feasibility of evaluating the comparative effectiveness and safety of electroacupuncture (EA) relative to manual acupuncture (MA) for the treatment of knee osteoarthritis (KOA). Methods: A multicenter randomized controlled clinical trial was conducted in Beijing from September 2017 to January 2018. A total of 60 participants with KOA were randomly allocated to either EA ( n = 30) or MA ( n = 30) groups. Participants in the EA group were treated with EA at six to seven local traditional acupuncture points or ah shi points, and two to three distal points. Participants in the MA group had the same schedule as the EA group except that the electrical apparatus featured a working power indicator without actual current output, constituting a sham EA procedure, in order to blind participants. Both groups received 24 sessions over 8 weeks. The primary outcome was response rate, defined as a change of ⩾50% from baseline in the total scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) after 8 weeks. Secondary outcomes included pain, stiffness, function, quality of life, and acupuncture-related adverse events (AEs) at 4 and 8 weeks. Results: Of 60 participants randomized, 53 (88%) completed the study. Response rates were 43% for the EA group and 30% for the MA group by the intention-to-treat analysis. Although significant differences were observed in WOMAC pain, stiffness, and function scores within both groups, between-group differences at 8 weeks did not reach statistical significance (odds ratio = 1.75 (95% confidence interval = 0.593–5.162)). Rates of AEs were low and similarly distributed between groups. Conclusion: Both EA and MA interventions in KOA were feasible and appeared safe. Whether or not EA may have a stronger impact on pain and function requires further evaluation through larger, adequately powered, randomized controlled trials. Trial registration number: NCT03274713.

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