Das Synovia-Volumen gesunder und arthrotischer menschlicher Kniegelenke*

Heilmann, H.-H.; Lindenhayn, K; Walther, H U

doi:10.1055/s-2008-1039786

Cited by 33 publications

(12 citation statements)

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“…In particular, the in vitro results showed that CG negatively affects chondrocyte viability and proliferation at 1.5 mg/mL, a concentration that, given the therapeutic protocol proposed for CG (two performed at 15 days apart and the third at one month after the last injection) and the volume of the synovial fluid in the symptomatic OA knee joint (>10 mL) [33,34], can never be reached in the clinical setting. These results are in contrast with previous observations by Furuzawa et al [17] who exposed cartilage tissue from five patients with OA for 7 days to 1% (0.6 µg/mL, MW unknown) porcine polymerized-collagen and observed a 3- to 6-fold increase in cell proliferation, but are consistent with those by Nakatani et al [35] who exposed ATDC5 cells, a murine chondrocyte cell line, to porcine hydrolyzed collagen (1 mg/mL) with an average molecular weight of 5 kDa and did not observe any effect on proliferation.…”

Section: Discussionmentioning

confidence: 99%

Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

Luca

Colombini

Carimati

et al. 2019

JCM

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Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed <3 kDa type I collagen has been developed and is currently available on the market as an injectable medical device. The primary objective of this study was to investigate the in vitro and in vivo effects of ChondroGrid in treating knee osteoarthritis symptoms to assess its safety and performance. Viability and proliferation of ChondroGrid-exposed human chondrocytes derived from five donors were assessed through the Alamar Blue/CyQuant assays. Their expression of MMP1/MMP3 and TIMP1/TIMP3 was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4mg/2mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.

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Section: Discussionmentioning

confidence: 99%

Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

Luca

Colombini

Carimati

et al. 2019

JCM

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“…Explants ( n = 7 per group) were cultured for 24 hours prior to assignment to one of the following treatment groups: 0.25% bupivacaine, 0.125% bupivacaine, 0.0625% bupivacaine, 1% lidocaine, 0.5% lidocaine, betamethasone acetate, methylprednisolone acetate, and triamcinolone. The concentration for each treatment group was based on the average volume of synovial fluid found in a human knee joint (7 mL) 13 and the volume of drug required to obtain the desired concentration ( Table 1 ). Explants were cultured in 1 mL of treatment or control media and incubated at 37°C with 5% CO 2 at 95% humidity for either 24 hours or 7 days.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Toxicity of Local Anesthetics and Corticosteroids on Chondrocyte and Synoviocyte Viability and Metabolism

et al. 2015

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Objective:There is growing concern that intra-articular injection of local anesthetic and/or corticosteroids may cause significant morbidity, including potential toxicity to chondrocytes and synoviocytes, after even a single exposure. We demonstrate that full thickness canine chondral and synovial samples exposed to various local anesthetics and corticosteroids exhibit decreased loss of cell viability compared with prior in vitro studies using monolayer culture, due to the protective effects of intact extracellular matrix and cell heterogeneity.Methods:Full-thickness cartilage and synovial explants were obtained from canine cadavers and exposed in culture media to the following for 24 hours: 1% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, 0.125% bupvacaine, 0.0625% bupivacaine, betamethasone acetate, methylprednisolone acetate, triamcinolone acetonide, or culture media only (control). Cell viability was determined on days 1 and 7 of culture using a microscopic live-dead and alamar blue metabolic assays.Results:Complete loss of chondrocyte and synoviocyte viability was noted in the 1% and 0.5% lidocaine group, 0.25% and 0.125% bupivacaine group, betamethasone group, and methylprednisolone groups after 1 and 7 days of culture. Treatment with 0.0625% bupivacaine and triamcinolone demonstrated no decrease in cell viability or metabolism when compared to negative control.Conclusions:In this canine explant model, 1% and 0.5% lidocaine, 0.25% and 0.125% bupivacaine, betamethasone acetate, and methylpresdnisolone acetate were severely chondrotoxic and synoviotoxic after a single exposure, despite intact extracellular matrix. In contrast, chondrocytes and synoviocytes exposed to 0.0625% bupivacaine and triamcinolone remained viable after treatment. Further in vivo study is needed before definitive recommendations can be made.

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“…Accumulation of large numbers of cartilage particles on the synovial intima could be further driven by increased synovial fluid effusion and turnover during OA. Even considering the reported concentrations of 100–500 particles/ml, with estimations of total volume and turnover rates for synovial fluid, millions of particles could accumulate on the synovium over the course of years of continuous cartilage degradation as OA progresses. It will be important for future work to understand the long‐term fate of wear particles in the joint, with respect to rates of generation and attachment to the synovial intima versus clearing via phagocytosis and enzymatic breakdown.…”

Section: Discussionmentioning

confidence: 99%

Cartilage Wear Particles Induce an Inflammatory Response Similar to Cytokines in Human Fibroblast‐Like Synoviocytes

Estell

Silverstein

Stefani

et al. 2019

Journal Orthopaedic Research

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The synovium plays a key role in the development of osteoarthritis, as evidenced by pathological changes to the tissue observed in both early and late stages of the disease. One such change is the attachment of cartilage wear particles to the synovial intima. While this phenomenon has been well observed clinically, little is known of the biological effects that such particles have on resident cells in the synovium. The present work investigates the hypothesis that cartilage wear particles elicit a pro-inflammatory response in diseased and healthy human fibroblast-like synoviocytes, like that induced by key cytokines in osteoarthritis. Fibroblast-like synoviocytes from 15 osteoarthritic human donors and a subset of three non-osteoarthritic donors were exposed to cartilage wear particles, interleukin-1α or tumor necrosis factor-α for 6 days and analyzed for proliferation, matrix production, and release of proinflammatory mediators and degradative enzymes. Wear particles significantly increased proliferation and release of nitric oxide, interleukin-6 and -8, and matrix metalloproteinase-9, -10, and -13 in osteoarthritic synoviocytes, mirroring the effects of both cytokines, with similar trends in non-osteoarthritic cells. These results suggest that cartilage wear particles are a relevant physical factor in the osteoarthritic environment, perpetuating the pro-inflammatory and pro-degradative cascade by modulating synoviocyte behavior at early and late stages of the disease. Future work points to therapeutic strategies for slowing disease progression that target cell-particle interactions.

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Das Synovia-Volumen gesunder und arthrotischer menschlicher Kniegelenke*

Cited by 33 publications

References 0 publications

Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

In Vitro Toxicity of Local Anesthetics and Corticosteroids on Chondrocyte and Synoviocyte Viability and Metabolism

Cartilage Wear Particles Induce an Inflammatory Response Similar to Cytokines in Human Fibroblast‐Like Synoviocytes

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