scholarly journals Developmental Mechanisms in Articular Cartilage Degradation in Osteoarthritis

Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Elena V. Tchetina
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Endochondral Ossification ◽  
Cartilage Degradation ◽  
Regulatory Mechanisms ◽  
Disease Development ◽  
Matrix Degradation ◽  
Chondrocyte Phenotype ◽  
Progressive Degeneration ◽  
Developmental Mechanisms

Osteoarthritis is the most common arthritic condition, which involves progressive degeneration of articular cartilage. The most recent accomplishments have significantly advanced our understanding on the mechanisms of the disease development and progression. The most intriguing is the growing evidence indicating that extracellular matrix destruction in osteoarthritic articular cartilage resembles that in the hypertrophic zone of fetal growth plate during endochondral ossification. This suggests common regulatory mechanisms of matrix degradation in OA and in the development and can provide new approaches for the treatment of the disease by targeting reparation of chondrocyte phenotype.

scholarly journals IL-10 reduces apoptosis and extracellular matrix degradation after injurious compression of mature articular cartilage

2016 ◽  
Vol 24 (11) ◽  
pp. 1981-1988 ◽  
Author(s):  
P. Behrendt ◽  
A. Preusse-Prange ◽  
T. Klüter ◽  
M. Haake ◽  
B. Rolauffs ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

scholarly journals Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF-β Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Rui Dong ◽  
Jun Ying ◽  
Taotao Xu ◽  
Songfeng Hu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Defect ◽  
Cartilage Degradation ◽  
Matrix Degradation ◽  
Chondrocyte Proliferation ◽  
Chondrocyte Hypertrophy ◽  
Articular Cartilage Repair ◽  
Genes Expression ◽  
Cells Cultured

Objective. To investigate the effect and underlying mechanism of Bushenhuoxue (BSHX) formula on articular cartilage repair. Methods. Twenty-four full-thickness cartilage defect rats were divided into two groups: model group and BSHX group (treated with BSHX formula). Macroscopic observation and histopathological study were conducted after 4- and 8-week treatment. Additionally, we also evaluated chondrocyte proliferation, extracellular matrix (ECM) deposition, cartilage degradation, and chondrocyte hypertrophy-related genes expression in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Moreover, we assessed aforementioned genes expression and pSMAD2/3 protein level in Tgfβr2 siRNA transfected chondrogenic ATDC5 cells in order to address whether BSHX formula exerts cartilage repairing effect through TGF-β signaling. Results. Neocartilage regeneration promotion effect was observed in cartilage defect rats after BSHX formula treatment, with increases in Col2 and pSMAD2 and decreases in Mmp13 and Runx2. Moreover, cell proliferation, the elevated Col2a1, Aggrecan and pSMAD2/3, reduced Mmp13, Adamts5, Col10a1, and Runx2 expression were also observed in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Besides, the expression alteration of ECM deposition, cartilage degradation, chondrocyte hypertrophy-related genes, and pSMAD2/3 protein levels presented in Tgfβr2 downregulated chondrogenic ATDC5 cells couldn’t be adjusted by BSHX formula treatment. Conclusion. By activation of TGF-β signaling, BSHX formula can promote articular cartilage repair by accelerating chondrocyte proliferation and maintaining chondrocyte phenotype, upregulate ECM accumulation, and inhibit matrix degradation.

scholarly journals Osteoarthritic Infrapatellar Fat Pad Aggravates Cartilage Degradation via Activation of p38MAPK and ERK1/2 Pathways

2020 ◽  
Author(s):  
Zuoqing Zhou ◽  
Su'an Tang ◽  
Xiaoyu Nie ◽  
Yiqun Zhang ◽  
Delong Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Degradation ◽  
Cartilage Explants ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Primary Chondrocytes ◽  
Tnf Α ◽  
And Cartilage ◽  
Human Primary Chondrocytes

Abstract Background: Although existing studies have suggested the involvement of the infrapatellar fat pad (IPFP) during the development of knee osteoarthritis (OA), the role of IPFP is still controversial. This study aimed to investigate the biochemical effects of osteoarthritic IPFP on cartilage and the underlying mechanisms.Methods: Human IPFP and articular cartilage were collected from end-stage OA patients during total knee arthroplasty. IPFP derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. CCK8 was used to detect the viability of human chondrocyte. qRT-PCR and western blotting was performed to evaluate the balance of extracellular matrix (ECM) catabolism and anabolism in human chondrocytes with FCM stimulation. Functional effect of osteoarthritic IPFP was also demonstrated in human articular cartilage by ex vivo assay. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Results: Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played a key role in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway.Conclusions: Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.

scholarly journals Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear

Cartilage ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 444-455 ◽  
Author(s):  
Robert L. Trevino ◽  
Carol A. Pacione ◽  
Anne-Marie Malfait ◽  
Susan Chubinskaya ◽  
Markus A. Wimmer
Keyword(s):  
Extracellular Matrix ◽  
Damage Model ◽  
Collagen Matrix ◽  
Cartilage Degradation ◽  
Matrix Degradation ◽  
Superficial Zone ◽  
Chondrocyte Viability ◽  
Damage Models ◽  
Damage Processes ◽  
The Impact

Background Many i n vitro damage models investigate progression of cartilage degradation after a supraphysiologic, compressive impact at the surface and do not model shear-induced damage processes. Models also neglect the response to uninterrupted tribological stress after damage. It was hypothesized that shear-induced removal of the superficial zone would accelerate matrix degradation when damage was followed by continued load and articulation. Methods Bovine cartilage underwent a 5-day test. Shear-damaged samples experienced 2 days of damage induction with articulation against polyethylene and then continued articulation against cartilage (CoC), articulation against metal (MoC), or rest as free-swelling control (FSC). Surface-intact samples were randomized to CoC, MoC, or FSC for the entire 5-day test. Samples were evaluated for chondrocyte viability, GAG (glycosaminoglycan) release (matrix wear surrogate), and histological integrity. Results Shear induction wore away the superficial zone. Damaged samples began continued articulation with collagen matrix disruption and increased cell death compared to intact samples. In spite of the damaged surface, these samples did not exhibit higher GAG release than intact samples articulating against the same counterface ( P = 0.782), contrary to our hypothesis. Differences in GAG release were found to be due to tribological testing against metal ( P = 0.003). Conclusion Shear-induced damage lowers chondrocyte viability and affects extracellular matrix integrity. Continued motion of either cartilage or metal against damaged surfaces did not increase wear compared with intact samples. We conjecture that favorable reorganization of the surface collagen fibers during articulation protected the underlying matrix. This finding suggests a potential window for clinical interventions to slow matrix degradation after traumatic incidents.

Anticatabolic Effects of Morin through the Counteraction of Interleukin-1β-Induced Inflammation in Rat Primary Chondrocytes

2019 ◽  
Vol 207 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Gyeong-Je Lee ◽  
In-A Cho ◽  
Ji-Su Oh ◽  
Yo-Seob  Seo ◽  
Jae-Seek You ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cellular Mechanism ◽  
Interleukin 1Β ◽  
Potential Candidate ◽  
Primary Chondrocytes ◽  
Progressive Degeneration ◽  
Herbal Plants ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Effect

Morin, a flavonoid isolated from various medicinal herbal plants, has an anti-inflammatory effect. This study aimed to elucidate the anticatabolic effects and cellular mechanism of morin against interleukin-1β (IL-1β) in rat primary chondrocytes. Morin at 10–100 μM did not affect the viability of rat primary chondrocytes. Treatment with morin for 21 days ameliorated the IL-1β-induced decrease in extracellular matrix. Furthermore, treatment with morin attenuated IL-1β-induced proteoglycan loss in the articular cartilage through suppression of catabolic factors, such as matrix metalloproteinases, inflammatory mediators, and pro-inflammatory cytokines. These data indicated that morin exerted anticatabolic effects that can prevent and reduce progressive degeneration of the articular cartilage, and thus may be a potential candidate treatment for osteoarthritis.

scholarly journals Icariin inhibits the inflammation through down-regulating NF-κB/HIF-2α signal pathways in chondrocytes

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Pengzhen Wang ◽  
Qingqi Meng ◽  
Wen Wang ◽  
Shaoheng Zhang ◽  
Xifeng Xiong ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Degradation ◽  
Cartilage Injury ◽  
Flavonoid Compound ◽  
Common Disease ◽  
Signal Pathways ◽  
Protective Effects ◽  
Chondrocyte Phenotype ◽  
Articular Cartilage Injury ◽  
Anti Inflammatory

Abstract Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In the present study, we confirmed the findings in our previous study that ICA promoted not only chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, the present study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

scholarly journals Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

2021 ◽  
Vol 22 (24) ◽  
pp. 13595
Author(s):  
Sophie Jane Gilbert ◽  
Cleo Selina Bonnet ◽  
Emma Jane Blain
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Proteolytic Enzymes ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Effect Change ◽  
Physiological Loading

The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans—decorin and biglycan—and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis. Specifically, we discuss studies that have characterised the response of articular cartilage to mechanical perturbations in the local tissue environment and how the magnitude or type of loading applied elicits cellular behaviours to effect change. In vivo, including transgenic approaches, and in vitro studies have illustrated how physiological loading maintains a homeostatic balance of anabolic and catabolic activities, involving the direct engagement of many PCM molecules in orchestrating this slow but consistent turnover of the cartilage matrix. Furthermore, we document studies characterising how abnormal, non-physiological loading including excessive loading or joint trauma negatively impacts matrix molecule biosynthesis and/or organisation, affecting PCM mechanical properties and reducing the tissue’s ability to withstand load. We present compelling evidence showing that reciprocal engagement of the cells with this altered ECM environment can thus impact tissue homeostasis and, if sustained, can result in cartilage degradation and onset of osteoarthritis pathology. Enhanced dysregulation of PCM/ECM turnover is partially driven by mechanically mediated proteolytic degradation of cartilage ECM components. This generates bioactive breakdown fragments such as fibronectin, biglycan and lumican fragments, which can subsequently activate or inhibit additional signalling pathways including those involved in inflammation. Finally, we discuss how bidirectionality within the ECM is critically important in enabling the chondrocytes to synthesise and release PCM/ECM molecules, growth factors, pro-inflammatory cytokines and proteolytic enzymes, under a specified load, to influence PCM/ECM composition and mechanical properties in cartilage health and disease.

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