scholarly journals Targeting Cartilage Degradation in Osteoarthritis

2021 ◽  
Vol 14 (2) ◽  
pp. 126
Author(s):  
Oliver McClurg ◽  
Ryan Tinson ◽  
Linda Troeberg
Keyword(s):  
Wnt Pathway ◽  
Cartilage Damage ◽  
Pharmaceutical Research ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Disease Modifying Drugs ◽  
Systemic Side Effects ◽  
Socio Economic Impact ◽  
Blocking Antibodies

Osteoarthritis is a common, degenerative joint disease with significant socio-economic impact worldwide. There are currently no disease-modifying drugs available to treat the disease, making this an important area of pharmaceutical research. In this review, we assessed approaches being explored to directly inhibit metalloproteinase-mediated cartilage degradation and to counteract cartilage damage by promoting growth factor-driven repair. Metalloproteinase-blocking antibodies are discussed, along with recent clinical trials on FGF18 and Wnt pathway inhibitors. We also considered dendrimer-based approaches being developed to deliver and retain such therapeutics in the joint environment. These may reduce systemic side effects while improving local half-life and concentration. Development of such targeted anabolic therapies would be of great benefit in the osteoarthritis field.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

scholarly journals Andrographis paniculata Extract Relieves Pain and Inflammation in Monosodium Iodoacetate-Induced Osteoarthritis and Acetic Acid-Induced Writhing in Animal Models

Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 873
Author(s):  
Donghun Lee ◽  
Chae Yun Baek ◽  
Ji Hong Hwang ◽  
Mi-Yeon Kim
Keyword(s):  
Acetic Acid ◽  
Weight Bearing ◽  
Cartilage Damage ◽  
Degenerative Joint Disease ◽  
Andrographis Paniculata ◽  
Joint Disease ◽  
Tnf Α ◽  
Monosodium Iodoacetate ◽  
History Of

Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats. Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1β, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.

LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis

Cartilage ◽  
2019 ◽  
pp. 194760351985575 ◽  
Author(s):  
Kang Chen ◽  
Hao Zhu ◽  
Min-Qian Zheng ◽  
Qi-Rong Dong
Keyword(s):  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Regulatory Function ◽  
Qrt Pcr ◽  
Ecm Degradation ◽  
Competitive Endogenous Rna

Background As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study’s aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA. Methods In the current study, chondrocytes were induced by interleukin-1β (IL-1β) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1β were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3. Results MEG3 was significantly downregulated in chondrocytes treated with IL-1β, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1β-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1β induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-β (TGF-β) signaling pathway, regulated chondrocytes ECM degradation in IL-1β induced chondrocytes subsequently. Conclusion LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.

scholarly journals New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 637 ◽  
Author(s):  
Paula Carpintero-Fernandez ◽  
Marta Varela-Eirin ◽  
Alessandra Lacetera ◽  
Raquel Gago-Fuentes ◽  
Eduardo Fonseca ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Molecular Model ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Novel Therapy ◽  
Human Cartilage ◽  
Sialic Acid Receptors ◽  
Cartilage Breakdown

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting α-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.

PPARγ preservation via promoter demethylation alleviates osteoarthritis in mice

2019 ◽  
Vol 78 (10) ◽  
pp. 1420-1429 ◽  
Author(s):  
Xiaobo Zhu ◽  
Fang Chen ◽  
Ke Lu ◽  
Ai Wei ◽  
Qing Jiang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Knockout Mice ◽  
Cartilage Damage ◽  
Critical Role ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Dna Methyltransferases ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Peroxisome Proliferator

ObjectivesOsteoarthritis (OA) is the most common degenerative joint disease in aged population and its development is significantly influenced by aberrant epigenetic modifications of numerous OA susceptible genes; however, the precise mechanisms that DNA methylation alterations affect OA pathogenesis remain undefined. This study investigates the critical role of epigenetic PPARγ (peroxisome proliferator–activated receptor-gamma) suppression in OA development.MethodsArticular cartilage expressions of PPARγ and bioactive DNA methyltransferases (DNMTs) from OA patients and mice incurred by DMM (destabilisation of medial meniscus) were examined. DNA methylation status of both human and mouse PPARγ promoters were assessed by methylated specific PCR and/or bisulfite-sequencing PCR. OA protections by a pharmacological DNA demethylating agent 5Aza (5-Aza-2'-deoxycytidine) were compared between wild type and PPARγ knockout mice.ResultsArticular cartilages from both OA patients and DMM mice display substantial PPARγ suppressions likely due to aberrant elevations of DNMT1 and DNMT3a and consequential PPARγ promoter hypermethylation. 5Aza known to inhibit both DNMT1 and DNMT3a reversed the PPARγ promoter hypermethylation, recovered the PPARγ loss and effectively attenuated the cartilage damage in OA mice. 5Aza also inhibited the OA-associated excessive inflammatory cytokines and deficit anti-oxidant enzymes, which were blocked by a specific PPARγ inhibitor in cultured chondrocytes. Further, 5Aza-confered protections against the cartilage damage and the associated abnormalities of OA-susceptible factors were significantly abrogated in PPARγ knockout mice.ConclusionEpigenetic PPARγ suppression plays a key role in OA development and PPARγ preservation via promoter demethylation possesses promising therapeutic potentials in clinical treatment of OA and the related joint diseases.

The Effect of the Prethanol Extract of Trifolium pratense Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

2018 ◽  
Vol 206 (1-2) ◽  
pp. 95-105 ◽  
Author(s):  
Seul Ah Lee ◽  
Sung-Min Moon ◽  
Seul Hee Han ◽  
Jae-Sung Kim ◽  
Do Kyung Kim ◽  
...  
Keyword(s):  
Trifolium Pratense ◽  
Nuclear Translocation ◽  
Red Clover ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Mitogen Activated Protein Kinase ◽  
Joint Disease ◽  
Griess Reagent ◽  
Mitogen Activated Protein ◽  
Cox 2

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by cartilage degradation and inflammation. The proinflammatory cytokine, interleukin (IL)-1β, plays a crucial role in the pathogenesis of OA by inducing the release of other catabolic factors that contribute to cartilage degradation. Trifolium pratense L. (red clover) has been used as a medicinal plant in many countries and as a source of nutraceuticals to alleviate the symptoms of menopause. Ob­jectives: In this study, we aimed to evaluate the anticatabolic effect of 40% prethanol extract of T. pratense (40% PeTP) on IL-1β-stimulated chondrocytes. Methods: Primary rat chondrocytes were pretreated with 40% PeTP for 1 h before stimulation with IL-1β (20 ng/mL). The production of nitrite, prostaglandin E2 (PGE2), and aggrecan was measured by using Griess reagent and ELISA. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4, mitogen-activated protein kinase (MAPK), and the nuclear factor (NF)-κB p65 subunit was measured by using Western blotting. Results: PeTP (40%) significantly inhibited the IL-1β-induced expression of nitrite, iNOS, PGE2, COX-2, MMP-1, MMP-3, MMP-13, and ADAMTS-4 in isolated primary rat chondrocytes. Furthermore, 40% PeTP decreased the IL-1β-induced degradation of aggrecan, the phosphorylation of MAPKs, and the nuclear translocation of the NF-κB p65 subunit. Conclusion: These results suggested that 40% PeTP has a chondroprotective effect on inflammation and may be a potential preventative agent for OA progression.

Chondroitin - application in the treatment of degenerative joint disease

2016 ◽  
Vol 18 (6) ◽  
pp. 621-628 ◽  
Author(s):  
Wiesław Tomaszewski
Keyword(s):  
Molecular Level ◽  
Proteolytic Enzymes ◽  
Chondroitin Sulphate ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Structural Elements ◽  
Acid Biosynthesis ◽  
Physiological Processes

Chondroitin is an organic compound, belonging to the group of glycosaminoglycans. In the treatment of degenerative joint disease, aka osteoarthritis, chondroitin sulphate is applied as a medicine or a dietary supplement. The biological importance of chondroitin sulphate has been already largely determined. The newest data on glycobiology research suggest that proteoglycans, as well as their complex polysaccharide macroparticles not only are the structural elements, but also they participate in multiple metabolic processes at a molecular level as well as in the physiological processes, regulating this type of mechanisms. The preparations applied in the treatment of degenerative joint disease, containing chondroitin sulphate, are attributed numerous therapeutic and chondroprotective properties including stabilizing synthesis processes and cartilage degradation through stimulation and inhibition of chondrocyte apoptosis (production of the elements of the intracellular substance and osteocyte stimulation), an increased proteoglycan and hyaluronic acid biosynthesis, inhibition of the activity of proteolytic enzymes and hyaluronidase, reduction of inflammatory mediators (prostaglandins and leukotrienes) and a decreased collagen II degradation. Based on the results of the multidirectional research available in the newest source literature, the analysis of the therapeutic efficacy and safety of chondroitin application in the treatment of degenerative joint disease was conducted.

Avulsion Fractures of the Femoral Head: Internal Fixation Using a Ventral Approach to the Hip Joint

1997 ◽  
Vol 10 (01) ◽  
pp. 23-26 ◽  
Author(s):  
P. M. Montavon ◽  
H. F. L’Eplattenier
Keyword(s):  
Femoral Head ◽  
Surgical Technique ◽  
Hip Joint ◽  
Cartilage Damage ◽  
Kirschner Wire ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Joint Surface ◽  
Avulsion Fractures ◽  
Lag Screw

SummaryAvulsion fractures of the femoral head are encountered in conjunction with craniodorsal luxations of the hip joint and cannot be treated conservatively without risking either reluxation of the joint or considerable cartilage damage resulting in degenerative joint disease. Fixation of the fragment is possible by inserting a Kirschner wire and a lag screw from the articular surface, making sure the implants are well countersunk. A ventromedial approach to the hip joint allows good visibility of the joint surface and easy reduction of the fracture without severing the round ligament. The surgical technique described was used on three cases and combines a ventromedial approach to the hip joint with fixation of the fracture with a Kirschner wire and a lag screw inserted from the joint surface, and has the advantages of enabling good reconstruction of the joint surface as well as maintaining postoperative joint stability. Both these factors considerably reduce the development of degenerative joint disease and improve the prognosis for recovery of full limb function.A surgical technique for treatment of avulsion fractures of the femoral head is described. It combines a ventromedial approach to the hip joint with fixation of the fracture with a Kirschner wire and a lag screw inserted from the joint surface.

Quantitative wear particle analysis for osteoarthritis assessment

2017 ◽  
Vol 231 (12) ◽  
pp. 1116-1126
Author(s):  
Meizhai Guo ◽  
Megan S Lord ◽  
Zhongxiao Peng
Keyword(s):  
Wear Debris ◽  
Wear Particle ◽  
Degradation Process ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Particle Analysis ◽  
Wear Particles ◽  
Wear Particle Analysis ◽  
Invasive Method

Osteoarthritis is a degenerative joint disease that affects millions of people worldwide. The aims of this study were (1) to quantitatively characterise the boundary and surface features of wear particles present in the synovial fluid of patients, (2) to select key numerical parameters that describe distinctive particle features and enable osteoarthritis assessment and (3) to develop a model to assess osteoarthritis conditions using comprehensive wear debris information. Discriminant analysis was used to statistically group particles based on differences in their numerical parameters. The analysis methods agreed with the clinical osteoarthritis grades in 63%, 50% and 61% of particles for no osteoarthritis, mild osteoarthritis and severe osteoarthritis, respectively. This study has revealed particle features specific to different osteoarthritis grades and provided further understanding of the cartilage degradation process through wear particle analysis – the technique that has the potential to be developed as an objective and minimally invasive method for osteoarthritis diagnosis.

Frictional Characteristics and Tissue Loss of Articular Cartilage Under a Novel Wear Regime

2007 ◽  
Author(s):  
Kelly J. Shields ◽  
John R. Owen ◽  
Jennifer S. Wayne
Keyword(s):  
Articular Cartilage ◽  
Articular Surface ◽  
Cartilage Damage ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Tissue Loss ◽  
Joint Function ◽  
Repair Technique ◽  
Repair Techniques

Degenerative joint disease, age, and trauma lead to progressive articular cartilage damage due to the tissue’s limited repair capabilities. Numerous clinical repair techniques with varying degrees of success have been developed in order to repair damaged tissue and restore joint function. One approach is the development of articular cartilage repair tissue to implant into the damaged or diseased articular surface. Determining the viability of an articular repair technique or tissue under in vivo stresses and wear is crucial to predict its success.

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