scholarly journals POS0393 FIBRIN DEPOSITION IS AN ACTIVE TRIGGER OF CARTILAGE DEGENERATION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 426.1-426
Author(s):  
T. Hügle ◽  
S. Nasi ◽  
D. Ehirchiou ◽  
P. Omoumi ◽  
A. So ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Explants ◽  
Fibrin Deposition ◽  
Qrt Pcr ◽  
Catabolic Genes ◽  
Key Factor ◽  
Calcific Deposits

Background:Fibrin(ogen) maintains inflammation in various disorders but has never been linked to cartilage damage in rheumatoid arthritis (RA) or other forms of inflammatory arthritis.Objectives:To investigate the role of fibrin deposition on cartilage integrity in arthritis.Methods:Fibrin deposition on knee cartilage was analyzed by immunohistochemistry in RA patients and in murine adjuvant-induced arthritis (AIA). In chondrocytes, fibrinogen expression (Fgα, Fgβ, Fgγ) and procoagulant activity were evaluated by qRT-PCR and turbidimetry respectively. Fibrin-induced catabolic genes were assessed by qRT-PCR in chondrocytes. Fibrin-mediated chondro-synovial adhesion (CSA) with subsequent cartilage tears was studied in co-cultures of human RA cartilage with autologous synoviocytes, in the AIA model, and by MRI. The link between fibrin and calcification was examined in human RA cartilage stained for calcific deposits and in vitro in fibrinogen-stimulated chondrocytes.Results:Fibrin deposition on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA wildtype (WT) mice, while fibrinogen deficient (Fg-/-) mice were protected. Accordingly, fibrin upregulated catabolic enzymes (Adamts5 and Mmp13) in chondrocytes. Secondly, CSA was present in fibrin-rich and damaged cartilage in AIA WT but not in Fg-/- mice. In line, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-positive degraded areas. Gadolinium-enhanced MRI of human joints showed contrast-enhancement along cartilage surface in RA patients but not in controls. Finally, fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization inducing pro-calcification genes (Anx5, Pit1, Pc1) and cytokine (IL-6). Although at a much lesser extent, we observed similar fibrin-mediated mechanisms in osteoarthritis (OA).Conclusion:Fibrin deposition directly impacts on cartilage integrity via induction of catabolism, mechanical stress, and calcification. Potentially, fibrin is a key factor of cartilage damage occurring in RA as a secondary consequence of inflammation.Disclosure of Interests:None declared

scholarly journals AB0092 FIBRIN ADHESION IS A PANNUS-INDEPENDENT MECHANISM OF CARTILAGE DEGENERATION IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1345.2-1346
Author(s):  
T. Hügle ◽  
S. Nasi ◽  
D. Ehirchiou ◽  
A. So ◽  
N. Busso
Keyword(s):  
Rheumatoid Arthritis ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Explants ◽  
Fibrin Deposition ◽  
Alizarin Red ◽  
Primary Chondrocytes ◽  
Qrt Pcr ◽  
Calcific Deposits

Background:Current concepts of cartilage destruction in inflammatory arthritis include pannus infiltration by inflamed synovial tissue as well as direct detrimental effects of inflammatory cytokines and proteinases. Fibrin maintains chronic inflammatory processes in arthritis but has never been shown to be directly involved in cartilage damage occurring in rheumatoid arthritis (RA).Objectives:To investigate fibrin-mediated cartilage degradation and the possible underlying mechanisms in arthritis.Methods:Human cartilage samples were obtained from patients with RA undergoing joint replacement and investigated by H.E. and immunohistochemistry for cartilage damage and fibrin deposition. Cartilage explants from RA patients were incubatedin vitrowith autologous synoviocytes and assessed by immunohistochemistry for cell-adhesion and colocalization with fibrin. Experimental RA was studied in the RA murine model of adjuvant-induced arthritis (AIA), in wildtype (WT) and fibrinogen deficient (Fg-/-) mice. Cartilage damage and chondro-synovial adhesion were analyzed by safranin-O staining and fibrin deposition by immunohistochemistry. Fibrinogen expression (Fgα, Fgβ, Fgɣ) was studied in murine primary chondrocytes by qRT-PCR. Cartilage explants were stained with alizarin-red staining and assessed for colocalization of calcific deposits and fibrin. Calcification of murine primary chondrocytes stimulated with secondary calciprotein particles (CPP) and treated with purified human plasma fibrinogen (100 µg/ml) was assessed by alizarin red staining and gene expression for chondrocytic differentiation (Agg, Coll2, Coll10, Sox9, Runx2), calcification (Alpl, Ank, Anx5, Pc1, Pit1, Pit2), and extracellular matrix remodeling (Adamts4, Adamts5, Mmp3, Mmp13, Comp) by qRT-PCR.Results:Abundant fibrin deposition on cartilage co-localized and positively correlated with cartilage damage in knee joints of patients with RA. In the AIA model, absence of fibrin deposition in Fg-/-mice was accompanied by significantly lower synovial inflammation, chondro-synovial adhesion and cartilage damage than in WT mice. Chondro-synovial adhesion correlated with cartilage damage in the WT and led to apparent mechanical stripping of the superficial cartilage, whilst this phenomenon was not observed in the Fg-/-mice.In vitro, autologous RA synoviocytes adhered to cartilage explants exclusively in the presence of fibrin deposition. Fibrinogen chains were not expressed by primary chondrocytes, indicating passive deposition from synovial fluid or tissue. In human RA cartilage explants, we found colocalization and a significant positive correlation between fibrin and calcific deposits. Fibrinogen caused exacerbated calcification in CPP-treated primary murine chondrocytes and induction of genes involved in chondrocyte calcification (Pc1, Pit1). Cartilage-oligomeric matrix protein (Comp) gene was also highly induced suggesting a pro-catabolic role of fibrinogen.Conclusion:Fibrin deposition is an active trigger of cartilage degeneration in RA via induction of chondro-synovial adhesion (mechanical aspect) and induction of calcification (catabolic aspect). Newer therapeutic approaches may not merely focus on fibrinolysis but protect cartilage from fibrin-induced adhesion or calcification e.g. by fibrin-targeted immunotherapy.Disclosure of Interests:Thomas Hügle Grant/research support from: Abbvie, Novartis, Consultant of: Abbvie, Pfizer, Novartis, Roche, Lilly, BMS, Sonia Nasi: None declared, Driss Ehirchiou: None declared, Alexander So Consultant of: Sobi, Grünenthal, Nathalie Busso: None declared

scholarly journals Autophagy Is Independent of the Chondroprotection Induced by Platelet-Rich Plasma Releasate

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Fan Yang ◽  
Haoran Hu ◽  
Wenjing Yin ◽  
Guangyi Li ◽  
Ting Yuan ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Interleukin 1 ◽  
Cartilage Degeneration ◽  
Inflammatory Stress ◽  
Catabolic Genes ◽  
Transmission Electron ◽  
Similar Expression Pattern ◽  
Vehicle Treatment

Background. Platelet-rich plasma (PRP) has been shown to be a promising therapeutic agent against osteoarthritis (OA), whereas its chondroprotection mechanism is not fully elucidated. Autophagy is considered an important biological process throughout the development of OA. Therefore, the objective of the present study is to investigate the role of autophagy in the chondroprotection and compare the effects of releasate between L-PRP and P-PRP. Methods. PRP were prepared from rat blood. Rat chondrocytes pretreated in the presence or absence of interleukin-1 beta (IL-1β) were incubated with PRP releasate. The expressions of OA-related genes and autophagy-related genes were determined by RT-PCR and western blot, respectively. Autophagic bodies were assessed by transmission electron microscopy and the autophagy flux was monitored under the confocal microscopy. The effect of PRP on autophagy was further investigated in the milieu of autophagy activator, rapamycin, or autophagy inhibition by downregulation of Atg5. The effect of PRP on cartilage repair and autophagy was also evaluated in an OA rat model. Results. In vitro, PRP releasate increased the expression of the anabolic genes, COL2 and Aggrecan, and decreased the expression of the catabolic genes, whereas the expression of autophage markers, Atg5 and Beclin-1, as well as the ratio of LC3 II/LC3 I, was not significantly altered in normal or IL-1β-treated chondrocytes. Similar expression pattern was found following the activation (rapamycin) or inhibition (Atg5 silencing) of autophagy. In vivo, PRP releasate ameliorated posttraumatic cartilage degeneration while the expression of LC3 was comparable to that in the vehicle treatment group. Conclusions. PRP releasate promoted the anabolic gene expression, relieved inflammatory stress in chondrocytes, and ameliorated cartilage degeneration, but autophagy was independent of these processes.

scholarly journals Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 162
Author(s):  
Xiaohua Chen ◽  
Bailing Zhou ◽  
Yan Gao ◽  
Kaiyu Wang ◽  
Jieping Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Efficiency ◽  
Cartilage Damage ◽  
Efficient Treatment ◽  
New Approach ◽  
Therapeutic Implications ◽  
Interfering Rna ◽  
Light Chain Enhancer ◽  
Made In

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide, causing severe cartilage damage and disability. Despite the recent progress made in RA treatment, limitations remain in achieving early and efficient therapeutic intervention. Advanced therapeutic strategies are in high demand, and siRNA-based therapeutic technology with a gene-silencing ability represents a new approach for RA treatment. In this study, we created a cationic delivery micelle consisting of low-molecular-weight (LMW) polyethylenimine (PEI)–cholesterol–polyethylene glycol (PEG) (LPCE) for small interfering RNA (siRNA)-based RA gene therapy. The carrier is based on LMW PEI and modified with cholesterol and PEG. With these two modifications, the LPCE micelle becomes multifunctional, and it efficiently delivered siRNA to macrophages with a high efficiency greater than 70%. The synthesized LPCE exhibits strong siRNA protection ability and high safety. By delivering nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 siRNA, the p65 siRNA/LPCE complex efficiently inhibited macrophage-based cytokine release in vitro. Local administration of the p65 siRNA/LPCE complex exhibited a fast and potent anti-inflammatory effect against RA in a mouse model. According to the results of this study, the functionalized LPCE micelle that we prepared has potential gene therapeutic implications for RA.

scholarly journals Biological Basis for the Use of Botanicals in Osteoarthritis and Rheumatoid Arthritis: A Review

2005 ◽  
Vol 2 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Salahuddin Ahmed ◽  
Jeremy Anuntiyo ◽  
Charles J. Malemud ◽  
Tariq M. Haqqi
Keyword(s):  
Rheumatoid Arthritis ◽  
Symptomatic Treatment ◽  
Cartilage Explants ◽  
Unknown Etiology ◽  
Joint Diseases ◽  
History Of ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Systemic Nature

Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects ∼1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports ∼60–90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely acceptedin vitromodels that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases.

scholarly journals CD11b Signaling Prevents Chondrocyte Mineralization and Attenuates the Severity of Osteoarthritis

2020 ◽  
Vol 8 ◽  
Author(s):  
Driss Ehirchiou ◽  
Ilaria Bernabei ◽  
Véronique Chobaz ◽  
Mariela Castelblanco ◽  
Thomas Hügle ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Cartilage Damage ◽  
Joint Disease ◽  
Crystal Formation ◽  
Cd11b Expression ◽  
Alizarin Red ◽  
Chondrocyte Hypertrophy ◽  
Qrt Pcr ◽  
Calciprotein Particles

Osteoarthritis (OA) is a progressive joint disease that is strongly associated with calcium-containing crystal formation (mineralization) by chondrocytes leading ultimately to cartilage calcification. However, this calcification process is poorly understood and treatments targeting the underlying disease mechanisms are lacking. The CD11b/CD18 integrin (Mac-1 or αMβ2), a member of the beta 2 integrin family of adhesion receptors, is critically involved in the development of several inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. We found that in a collagen-induced arthritis, CD11b-deficient mice exhibited increased cartilage degradation compared to WT control animals. However, the functional significance of CD11b integrin signaling in the pathophysiology of chondrocytes remains unknown. CD11b expression was found in the extracellular matrix and in chondrocytes in both healthy and damaged human and murine articular cartilage. Primary murine CD11b KO chondrocytes showed increased mineralization when induced in vitro by secondary calciprotein particles (CPP) and quantified by Alizarin Red staining. This increased propensity to mineralize was associated with an increased alkaline phosphatase (Alp) expression (measured by qRT-PCR and activity assay) and an enhanced secretion of the pro-mineralizing IL-6 cytokine compared to control wild-type cells (measured by ELISA). Accordingly, addition of an anti-IL-6 receptor antibody to CD11b KO chondrocytes reduced significantly the calcification and identified IL-6 as a pro-mineralizing factor in these cells. In the same conditions, the ratio of qRT-PCR expression of collagen X over collagen II, and that of Runx2 over Sox9 (both ratio being indexes of chondrocyte hypertrophy) were increased in CD11b-deficient cells. Conversely, the CD11b activator LA1 reduced chondrocyte mineralization, Alp expression, IL-6 production and collagen X expression. In the meniscectomy (MNX) model of murine knee osteoarthritis, deficiency of CD11b led to more severe OA (OARSI scoring of medial cartilage damage in CD11b: 5.6 ± 1.8, in WT: 1.2 ± 0.5, p < 0.05, inflammation in CD11b: 2.8 ± 0.2, in WT: 1.4 ± 0.5). In conclusion, these data demonstrate that CD11b signaling prevents chondrocyte hypertrophy and chondrocyte mineralization in vitro and has a protective role in models of OA in vivo.

scholarly journals LncRNA CRNED Hinders The Progression of Osteoarthritis By Epigenetic Regulation of DACT1

2021 ◽  
Author(s):  
Ziqi Zhang ◽  
Pei Yang ◽  
Chunsheng Wang ◽  
Run Tian
Keyword(s):  
Rat Model ◽  
Epigenetic Modification ◽  
Colorectal Neoplasia ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Downstream Target ◽  
Age Related

Abstract Osteoarthritis (OA) is mainly characterized by articular cartilage degeneration, synovial fibrosis, and inflammation. LncRNA CRNED (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored. In this study, an OA rat model was established by using anterior cruciate ligament transection, and the adenovirus-mediated CRNED overexpression (Ad-CRNED) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were injected into the rat model via tail vein. Besides, chondrocyte‑like ATDC5 cells were treated with IL-1β (10 ng/mL) to simulate OA conditions in vitro. We found that overexpression of CRNED alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in chondrocyte‑like ATDC5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNED both in vivo and in vitro. Mechanism studies revealed that DACT1 could act as a downstream target of CRNED. By recruiting p300, CRNED promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNED hindered the activation of the Wnt/β-catenin pathway in IL-1β-stimulated cells by inducing DACT1 expression. In conclusion, CRNED promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.

Interleukin-1β Is Essential for Blood-Induced Cartilage Damage In Vitro

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 240-240
Author(s):  
Lize F.D. van Vulpen ◽  
Goris Roosendaal ◽  
Simon C. Mastbergen ◽  
Floris P.J.G. Lafeber ◽  
Roger E.G. Schutgens
Keyword(s):  
Blood Donors ◽  
Cartilage Damage ◽  
Time Dependent ◽  
Cartilage Explants ◽  
Proteoglycan Synthesis ◽  
Synthesis Rate ◽  
Cartilage Proteoglycan ◽  
Significant Difference ◽  
Dose Dependent

Abstract Objective: Joint damage due to recurrent joint bleeds remains the most common complication in hemophilia. The combination of cartilage degeneration and synovial inflammation ultimately lead to hemophilic arthropathy. Cartilage destruction is considered to result from both cartilage matrix-degrading proteases as well as cartilage-destructive pro-inflammatory cytokines such as interleukin (IL)-1b. To unravel the role of IL1b in the pathogenesis of blood-induced cartilage damage, we investigated whether direct blocking of IL1b specifically prevents blood-induced cartilage damage in vitro. Moreover, we investigated whether blocking IL1b after the onset of a bleed can still avert cartilage damage. Methods: Full thickness healthy human articular cartilage explants, obtained post-mortem, were cultured for four days in presence or absence of 50% v/v whole blood. A recombinant human IL1b monoclonal antibody (IL1bmAb) was added at the moment of blood exposure in a concentration of 0, 1, 3, 10, 30, or 100ng/mL (n=8). Furthermore, 100ng/mL IL1bmAb was administered directly or after a delay of several hours up to two days (n=7). Cartilage matrix proteoglycan turnover was determined 12 days later to analyse long-term effects. To investigate the direct effects of IL1bmAb on cartilage, explants were cultured for four days in the presence of 10ng/mL IL1bmAb in the absence of blood (n=7). Results: Exposure to blood decreased the proteoglycan synthesis rate and -content, and increased the proteoglycan release (all p<0.05). Adding IL1bmAb resulted in a dose-dependent increase of the proteoglycan synthesis rate leading to normalisation at higher concentrations (see figure A). Proteoglycan release and –content also normalised after addition of IL1bmAb. Its protective effect was most pronounced when IL1bmAb was administered within 4 hours after the bleed, but significant recovery was still achieved by administration within 8-24 hours (see figure B for proteoglycan synthesis). In the absence of blood, IL1bmAb did not have direct effects on cartilage proteoglycan turnover (for all three parameters p>0.50). Conclusions: This study demonstrates that IL1b is a crucial factor in the development of blood-induced cartilage damage in vitro. Blocking this pro-inflammatory cytokine with a monoclonal antibody protects cartilage from the damaging effects of blood exposure in a dose-dependent way. Early administration after blood-exposure is most beneficial. Further research is warranted to investigate the in vivo capacity of IL1bmAb in prevention and its position as a treatment to limit joint damage upon joint bleeding. Figure - Effect of IL1bmAb on cartilage proteoglycan synthesis rate is dose-dependent (A) and time-dependent (B). Median values ± IQR of at least 7 individual cartilage and blood donors are shown. Hash tags indicate a statistically significant difference from control values, whereas asterisks indicate a statistically significant difference from blood-exposed cartilage without IL1bmAb addition (p<0.05). Figure -. Effect of IL1bmAb on cartilage proteoglycan synthesis rate is dose-dependent (A) and time-dependent (B). Median values ± IQR of at least 7 individual cartilage and blood donors are shown. Hash tags indicate a statistically significant difference from control values, whereas asterisks indicate a statistically significant difference from blood-exposed cartilage without IL1bmAb addition (p<0.05). Figure - Effect of IL1 b mAb on cartilage proteoglycan synthesis rate is dose-dependent (A) and time-dependent (B). Median values ± IQR of at least 7 individual cartilage and blood donors are shown. Hash tags indicate a statistically significant difference from control values, whereas asterisks indicate a statistically significant difference from blood-exposed cartilage without IL1 b mAb addition (p<0.05). Disclosures Schutgens: CSL Behring: Research Funding.

ILThe Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-κB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

2013 ◽  
Vol 68 (7-8) ◽  
pp. 336-342
Author(s):  
Mathias Glehr ◽  
Margherita Breisach ◽  
Sonja Walzer ◽  
Birgit Lohberger ◽  
Florentine Fürst ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinases ◽  
Nuclear Factor Κb ◽  
Qrt Pcr ◽  
Pharmacological Studies ◽  
Receptor Activator ◽  
Polymerase Chain ◽  
Fibroblast Like Synoviocytes

Medication of rheumatoid arthritis (RA) remains challenging and often controversial concerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-inflammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fibroblast-like synoviocytes (FLS). Interleukin-1β- stimulated RA-FLS were treated with 100 μM resveratrol for 24 h. To evaluate the effect of resveratrol on the amount of bound/combined MMPs, a Luminex® xMAP multiplexing technology was used. The alteration in expression of receptor activator of nuclear factor- κB ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Resveratrol reduced the expression of MMP-1 (p = 0.022), MMP-3 (p = 0.021), and MMP-9 (p = 0.047). qRT-PCR showed a significant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018). Our in vitro findings indicate that resveratrol could be a new target for further pharmacological studies in the field of RA. In the future it could play a role as a possible substitute or supplement to currently used drugs against RA to prevent cartilage matrix degradation and pathological bone resorption due to inhibition of MMPs and RANKL

scholarly journals Chondroprotective Potential of Fruit Extracts ofPhyllanthus emblicain Osteoarthritis

2008 ◽  
Vol 5 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Venil N. Sumantran ◽  
Asavari Kulkarni ◽  
Rucha Chandwaskar ◽  
Abhay Harsulkar ◽  
Bhushan Patwardhan ◽  
...  
Keyword(s):  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Hot Water ◽  
Cartilage Explants ◽  
Aqueous Extracts ◽  
Glucosamine Sulphate ◽  
Fruit Powder ◽  
Set Up

There is a need for effective nutraceuticals for osteoarthritis care. The fruit ofPhyllanthus emblicais used as a powerful rejuvenator in Ayurvedic medicine. This study measured the chondroprotective potential ofP. emblica(‘Amalaki’) fruitsin vitro. We used aqueous extracts of unprocessedP. emblicafruit powder (powder A), and the powder obtained after hot water extraction and drying of powder A (powder B). Chondroprotection was measured in three different assay systems. First, we tested the effects of both fruit powders on the activities of the enzymes hyaluronidase and collagenase type 2. Second, anin vitromodel of cartilage degradation was set-up with explant cultures of articular knee cartilage from osteoarthritis patients. Cartilage damage was assayed by measuring glycosaminoglycan release from explants treated with/withoutP. emblicafruit powders. Aqueous extracts of both fruit powders significantly inhibited the activities of hyaluronidase and collagenase type 2in vitro. Third, in the explant model of cartilage matrix damage, extracts of glucosamine sulphate and powder B (0.05 mg/ml) exhibited statistically significant, long-term chondroprotective activity in cartilage explants from 50% of the patients tested. This result is important since glucosamine sulphate is the leading nutraceutical for osteoarthritis. Powder A induced a statistically significant, short-term chondroprotective activity in cartilage explants from all of the patients tested. This is the first study to identify and quantitate new chondroprotective activities ofP. emblicafruits. These data provide pilot pre-clinical evidence for the use ofP. emblicafruits as a chondroprotective agent in osteoarthritis therapy.

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