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Effect of intra-articular hyaluronan injection on inflammation and bone remodeling in the epiphyses and metaphyses of the knee in a murine model of joint injury.

ABSTRACT: The TTR (transforming growth factor ?1 (TGF?1) injection with treadmill running) model of murine joint injury was used to examine effects of intra-articular Hyaluronan (IA HA) on the metabolism of subchondral bone. HA was injected 24 h after TGF?1 injection and its effects on the mRNA of 80 genes in the Nfkb pathway, and bone remodeling genes, Acp5, Nos2 and Arg1, in femoral and tibial epiphyses/metaphyses of injected and contralateral legs was assessed. Structural bone parameters at those sites were determined by Micro-computed tomography (micro CT) and bone remodeling cells identified with histochemistry for tartrate-resistant acid phosphatase and immunohistochemistry for Nitric oxide synthase 2 (NOS2) and Arginase 1. Gene expression responses in femoral compartments were generally inhibitory and notably biphasic whereas the tibia was relatively non-responsive. Gene expression was also altered in the contralateral femoral compartment but were predominantly activated. IA TGFb did not alter bone structure in the injected leg, but resulted in a statistically significant reduction (25-40%) in trabecular bone of the contralateral limb. IA HA did not affect such changes. This bone loss was associated with an acute decrease in transcript abundance for Acp5, Nos2, Arg1 and this decrease persisted for Nos2 and Arg1. In conclusion, the data illustrate that in this model, IA TGF?1 injection results in marked biphasic changes in NfKb-regulated apoptosis, IL1 and IL12 pathways, which were transiently altered after IA HA therapy. The finding that all modulations are essentially restricted to the femoral compartment is consistent with the predominant localization and clearance of injected HA from this site.

SUBMITTER: Shen Q

PROVIDER: S-EPMC6614662 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effect of intra-articular hyaluronan injection on inflammation and bone remodeling in the epiphyses and metaphyses of the knee in a murine model of joint injury.

Shen Quan Q Li Jun J Chan Deva D Sandy John D JD Takeuchi Jun J Ross Ryan D RD Plaas Anna A

American journal of translational research 20190615 6

The TTR (transforming growth factor β1 (TGFβ1) injection with treadmill running) model of murine joint injury was used to examine effects of intra-articular Hyaluronan (IA HA) on the metabolism of subchondral bone. HA was injected 24 h after TGFβ1 injection and its effects on the mRNA of 80 genes in the Nfkb pathway, and bone remodeling genes, <i>Acp5, Nos2</i> and <i>Arg1</i>, in femoral and tibial epiphyses/metaphyses of injected and contralateral legs was assessed. Structural bone parameters ...[more]

PMID: 31312344

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Project description:IntroductionIntra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain.MethodsThis study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24 hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle.Ethics approval and disseminationThis study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration numberClinicalTrials.gov Identifier: NCT04117893; Pre-results.

Project description:BackgroundRecently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid.MethodsUsing hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years.ResultsOn the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5).ConclusionsSevere osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA.Trial registrationThe study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Project description:BackgroundAs an essential component of multimodal analgesia approaches after total knee arthroplasty (TKA), local infiltration analgesia (LIA) can be classified into peri-articular injection (PAI) and intra-articular injection (IAI) according to administration techniques. Currently, there is no definite answer to the optimal choice between the two techniques. Our study aims to investigate analgesic efficacy and safety of PAI versus IAI in patients receiving simultaneous bilateral TKA.MethodsThis randomized controlled trial was conducted from February 2017 and finished in July 2018. Sixty patients eligible for simultaneous bilateral total knee arthroplasty were randomly assigned to receive PAI on one side and IAI on another. Primary outcomes included numerical rating scale (NRS) pain score at rest or during activity at 3?h, 6?h, 12?h, 24?h, 48?h, and 72?h following surgery. Secondary outcomes contained active or passive range of motion (ROM) at 1, 2, and 3?days after surgery, time to perform straight leg raise, wound drainage, operation time, and wound complications.ResultsPatients experienced lower NRS pain scores of the knee receiving PAI compared with that with PAI during the first 48?h after surgery. The largest difference of NRS pain score at rest occurred at 48?h (PAI: 0.68, 95%CI[0.37, 0.98]; IAI: 2.63, 95%CI [2.16, 3.09]; P <?0.001); and the largest difference of NRS pain score during activity also took place at 48?h (PAI: 2.46, 95%CI [2.07, 2.85]; IAI: 3.90, 95%CI [3.27, 4.52]; P =?0.001). PAI group had better results of range of motion and time to perform straight leg raise when compared with IAI group. There were no differences in operation time, wound drainage, and wound complication.ConclusionPAI had the superior performance of pain relief and improvement of range of motion to IAI. Therefore, the administration technique of peri-articular injection is recommended when performing local infiltration analgesia after total knee arthroplasty.Trial registrationThe trial was retrospectively registered in the Chinese Clinical Trial Registry as ChiCTR1800020420 on 29th December, 2018.Level of evidenceTherapeutic Level I.

Dataset Information

Effect of intra-articular hyaluronan injection on inflammation and bone remodeling in the epiphyses and metaphyses of the knee in a murine model of joint injury.

Publications

Effect of intra-articular hyaluronan injection on inflammation and bone remodeling in the epiphyses and metaphyses of the knee in a murine model of joint injury.

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