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Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

ABSTRACT: Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish the value of intra-articular injections of polyphenol in stabilization of cartilage collagen against degradation and indicate the unique beneficial role of injectable polyphenols in protecting the cartilage in arthritic conditions.

SUBMITTER: Natarajan V

PROVIDER: S-EPMC4457493 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

Natarajan Venkatachalam V Madhan Balaraman B Tiku Moti L ML

PloS one 20150605 6

Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crossli ...[more]

PMID: 26046639

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Project description:BackgroundIntra-articular (IA) corticosteroid (CS) injections are the mainstay of treatment for symptomatic management in knee osteoarthritis (OA), particularly in the UK. IA platelet-rich plasma (PRP) injections are a promising alternative, but no systematic reviews to date have compared them to the current standard of care, IA CS injections. We aim to investigate the effect of IA PRP injections versus IA corticosteroid injections for the symptomatic management of knee OA.MethodsAll published trials comparing IA PRP and CS injections for knee OA were included. MEDLINE, EMBASE, Scopus and Web of Science were searched through June 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random effects model was used to calculate standardized mean difference with 95% confidence interval in WOMAC/VAS score (or subscores), comparing IA PRP to CS injections across studies.ResultsIncluded were eight studies and 648 patients, 443 (68%) were female, mean age 59 years, with a mean BMI of 28.4. Overall, the studies were considered at low risk of bias. Compared with CS injections, PRP was significantly better in reducing OA symptoms (pain, stiffness, functionality) at 3, 6 and 9 months post-intervention (P < 0.01). The greatest effect was observed at 6 and 9 months (- 0.78 (- 1.34 to - 0.23) standard mean deviations (SMD) and - 1.63 (- 2.14 to - 1.12) SMD respectively). At 6 months, this equates to an additional reduction of 9.51 in WOMAC or 0.97 on the VAS pain scales. At 6 months PRP allowed greater return to sporting activities than CS, measured by the KOOS subscale for sporting activity, of magnitude 9.7 (- 0.45 to 19.85) (P = 0.06). Triple injections of PRP, generally separated by a week, were superior to single injections over 12 months follow-up (P < 0.01).ConclusionsIA-PRP injections produce superior outcomes when compared with CS injections for symptomatic management of knee OA, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. Giving three IA-PRP, with injections separated by a week, appears more effective than 1 IA-PRP injection.Prospero trial registration numberCRD42020181928 .

Project description:BackgroundCartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation.PurposeTo evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model.Study designControlled laboratory study.MethodsA full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mice (N = 80). Mice received an intra-articular injection of TAA or saline on day 1 or 7 after induction of the defect. Mice were euthanized on days 10 and 28 for histological evaluation of cartilage defect repair, synovial inflammation, and synovial membrane thickness.ResultsMice injected with TAA had significantly less synovial inflammation at day 10 than saline-injected mice independent of the time of administration. At day 28, the levels of synovitis dropped toward healthy levels; nevertheless, the synovial membrane was thinner in TAA- than in saline-injected mice, reaching statistical significance in animals injected on day 1 (70.1 ± 31.9 µm vs 111.9 ± 30.9 µm, respectively; P = .01) but not in animals injected on day 7 (68.2 ± 21.86 µm vs 90.2 ± 21.29 µm, respectively; P = .26). A thinner synovial membrane was moderately associated with less filling of the defect after 10 and 28 days (r = 0.42, P = .02; r = 0.47, P = .01, respectively). Whereas 10 days after surgery there was no difference in the area of the defect filled and the cell density in the defect area between saline- and TAA-injected knees, filling of the defect at day 28 was lower in TAA- than in saline-injected knees for both injection time points (day 1 injection, P = .04; day 7 injection, P = .01). Moreover, there was less collagen type 2 staining in the filled defect area in TAA- than in saline-injected knees after 28 days, reaching statistical significance in day 1-injected knees (2.6% vs 18.5%, respectively; P = .01) but not in day 7-injected knees (7.4% vs 15.8%, respectively; P = .27).ConclusionIntra-articular injection of TAA reduced synovial inflammation but negatively affected cartilage repair. This implies that inhibition of inflammation may inhibit cartilage repair or that TAA has a direct negative effect on cartilage formation.Clinical relevanceOur findings show that TAA can inhibit cartilage defect repair. Therefore, we suggest not using TAA to reduce inflammation in a cartilage repair setting.

Project description:Purpose ?The aim of the study was to evaluate the clinical effects of HYADD® 4, an hydrogel based on a hyaluronic acid derivative, in patients with symptomatic knee osteoarthritis, on symptoms, and joint function. Methods ?This retrospective study of patients with Kellgren-Lawrence grade II to IV knee osteoarthritis (American College of Rheumatology criteria) enrolled patients who had received two infiltrations of HYADD® 4, (24 mg/3 mL) 1?week apart, and evaluated: pain at rest, pain with movement, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score; change in nonsteroidal anti-inflammatory drugs (NSAIDs)/acetaminophen use; satisfaction with therapy; tolerability. Study duration was 6 months for all predefined endpoints, with a 6-month extension for pain symptoms only. Results ?After 6 months, all predefined endpoints were evaluable in 698 of 937 enrolled patients (74.5%). Mean WOMAC scores were reduced by 56.3% from baseline ( p ?<?0.05). NSAIDs/acetaminophen use ?2 times/week (48.8% of patients at baseline) was substantially reduced after 1?month and was 19.6% after 6 months. After 6 months, 85.6% of patients were satisfied about efficacy. There were no significant adverse effects. The effect on resting pain was rapid, strong, and lasting: reduction from baseline was 45.1% at 1?month ( p ?<?0.05), 56.8% at 6 months ( p ?<?0.05), and 53.6% at 12 months ( p ?<?0.05). Pain on moving was reduced by 47.4% after 6 months ( p ?<?0.05) and 46.0% after 12 months ( p ?<?0.05), results at 6 and 12 months were similar. Conclusion ?HYADD® 4 is a new-generation hyaluronic acid with distinctive viscoelastic and rheological properties. In patients with mild-to-severe knee OA (Kellgren-Lawrence grades II-IV), two consecutive infiltrations 1?week apart reduced WOMAC scores and NSAIDs/acetaminophen consumption for at least 6 months. In a subpopulation ( n ?=?106), efficacy on pain lasted approximately 12 months. Adverse events were reported in 11.2% of patients; the most frequent were arthralgias. No cases of allergic reactions or systemic effects were recorded. Level of Evidence ?Level IV, retrospective case series.

Dataset Information

Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

Publications

Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.

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