Blocking Wnt/β-Catenin Signaling Alleviates Osteoarthritis in Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 704-708
Author(s):  
Ying Wang ◽  
Lili Sun ◽  
Junli Qin ◽  
Meng Wu ◽  
Jinfeng Zhang
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Cartilage Damage ◽  
Iodoacetic Acid ◽  
Protective Role ◽  
Joint Disease ◽  
Cartilage Tissue ◽  
Blue Staining ◽  
Real Time Quantitative Pcr ◽  
Safranin O

Osteoarthritis is a chronic multiple degenerative bone and joint disease. The most common manifestations are damaged articular cartilage, thickening and sclerosis of subchondral bone, and osteophytes formation at the joint edge. This study will block the Wnt/β -catenin signaling pathway to observe its role on a rat model of osteoarthritis. In this experiment, rat osteoarthritis model was established by intra-articular administration of iodoacetic acid. The LF-3 treatment was started on the second day after modeling. Two weeks later, rat knee articular cartilage was collected. The morphology of cartilage was observed by HE, Safranin O and toluidine blue staining. The expression levels of TIMP-3, MMP-9 protein and mRNA were detected by western blot and real-time quantitative PCR. After blocking the Wnt/ β-catenin signaling pathway, TIMP-3 expression level was increased, MMP-9 expression was decreased, and cartilage damage was ameliorated. Blocking the Wnt/ β-catenin signal can reduce the degradation of matrix in cartilage tissue, thereby playing a protective role and helping the recovery of osteoarthritic rats.

scholarly journals Immunochemical and Mechanical Characterization of Cartilage Subtypes in Rabbit

2002 ◽  
Vol 50 (8) ◽  
pp. 1049-1058 ◽  
Author(s):  
Andreas Naumann ◽  
James E. Dennis ◽  
Amad Awadallah ◽  
David A. Carrino ◽  
Joseph M. Mansour ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Tissue ◽  
Blue Staining ◽  
Joint Analysis ◽  
Type I ◽  
Auricular Cartilage ◽  
Collagen Types ◽  
Type Vi Collagen ◽  
Intense Staining ◽  
Nasal Cartilage

Cartilage is categorized into three general subgroups, hyaline, elastic, and fibrocartilage, based primarily on morphologic criteria and secondarily on collagen (Types I and II) and elastin content. To more precisely define the different cartilage subtypes, rabbit cartilage isolated from joint, nose, auricle, epiglottis, and meniscus was characterized by immunohistochemical (IHC) localization of elastin and of collagen Types I, II, V, VI, and X, by biochemical analysis of total glycosaminoglycan (GAG) content, and by biomechanical indentation assay. Toluidine blue staining and safranin-O staining were used for morphological assessment of the cartilage subtypes. IHC staining of the cartilage samples showed a characteristic pattern of staining for the collagen antibodies that varied in both location and intensity. Auricular cartilage is discriminated from other subtypes by interterritorial elastin staining and no staining for Type VI collagen. Epiglottal cartilage is characterized by positive elastin staining and intense staining for Type VI collagen. The unique pattern for nasal cartilage is intense staining for Type V collagen and collagen X, whereas articular cartilage is negative for elastin (interterritorially) and only weakly positive for collagen Types V and VI. Meniscal cartilage shows the greatest intensity of staining for Type I collagen, weak staining for collagens V and VI, and no staining with antibody to collagen Type X. Matching cartilage samples were categorized by total GAG content, which showed increasing total GAG content from elastic cartilage (auricle, epiglottis) to fibrocartilage (meniscus) to hyaline cartilage (nose, knee joint). Analysis of aggregate modulus showed nasal and auricular cartilage to have the greatest stiffness, epiglottal and meniscal tissue the lowest, and articular cartilage intermediate. This study illustrates the differences and identifies unique characteristics of the different cartilage subtypes in rabbits. The results provide a baseline of data for generating and evaluating engineered repair cartilage tissue synthesized in vitro or for post-implantation analysis.

scholarly journals Hydrogels for the Application of Articular Cartilage Tissue Engineering: A Review of Hydrogels

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Er-Yuan Chuang ◽  
Chih-Wei Chiang ◽  
Pei-Chun Wong ◽  
Chih-Hwa Chen
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Cartilage Damage ◽  
Medical Science ◽  
Cartilage Tissue Engineering ◽  
Polymeric Materials ◽  
Tissue Growth ◽  
Cartilage Tissue ◽  
Cellular Interaction ◽  
Polymeric Hydrogels

The treatment of articular cartilage damage is a major task in the medical science of orthopedics. Hydrogels possess the ability to form multifunctional cartilage grafts since they possess polymeric swellability upon immersion in an aqueous phase. Polymeric hydrogels are capable of physiological swelling and greasing, and they possess the mechanical behavior required for use as articular cartilage substitutes. The chondrogenic phenotype of these materials may be enhanced by embedding living cells. Artificial hydrogels fabricated from biologically derived and synthesized polymeric materials are also used as tissue-engineering scaffolds; with their controlled degradation profiles, the release of stimulatory growth factors can be achieved. In order to make use of these hydrogels, cartilage implants were formulated in the laboratory to demonstrate the bionic mechanical behaviors of physiological cartilage. This paper discusses developments concerning the use of polymeric hydrogels for substituting injured cartilage tissue and assisting tissue growth. These gels are designed with consideration of their polymeric classification, mechanical strength, manner of biodegradation, limitations of the payload, cellular interaction, amount of cells in the 3D hydrogel, sustained release for the model drug, and the different approaches for incorporation into adjacent organs. This article also summarizes the different advantages, disadvantages, and the future prospects of hydrogels.

Puerarin Attenuates Osteoarthritis via Upregulating AMP-Activated Protein Kinase/Proliferator-Activated Receptor-γ Coactivator-1 Signaling Pathway in Osteoarthritis Rats

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 117-125 ◽  
Author(s):  
Luyao Wang ◽  
Haojie Shan ◽  
Bin Wang ◽  
Nan Wang ◽  
Zubin Zhou ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Cartilage Damage ◽  
Joint Disease ◽  
Mitochondrial Dysfunctions ◽  
Compound C ◽  
Amp Activated Protein Kinase ◽  
And Cartilage

Background/Aims: Osteoarthritis is the most common degenerative joint disease and causes major pain and disability in adults. It has been reported that mitochondrial dysfunction in chondrocytes was associated with osteoarthritis. Puerarin has multiple effects including restoring mitochondrial function. In this study, the potential effects of puerarin on osteoarthritis and osteoarthritis associated mitochondrial dysfunctions were evaluated. Methods: Osteoarthritis rats were treated with puerarin and the severity of osteoarthritis and cartilage damages was evaluated. The mitochondrial biogenesis and functions were analyzed by measuring related proteins expression, mitochondrial DNA content, ATP production, and oxygen consumption. The dependence of AMP-activated protein kinase (AMPK) pathway on puerarin-regulated mitochondrial function was analyzed by applying AMPK inhibitor Compound C. Results: Puerarin treatment alleviated mechanical hyperalgesia and cartilage damage in osteoarthritis rats. Puerarin increased mitochondrial biogenesis and attenuated mitochondrial dysfunctions in osteoarthritis rats. AMPK inhibitor Compound C abolished puerarin’s effects. Conclusion: Puerarin attenuates osteoarthritis by upregulating the AMPK/proliferator-activated receptor-γ coactivator signaling pathway in osteoarthritis rats.

scholarly journals Blockade of TRPM7 Alleviates Chondrocyte Apoptosis and Articular Cartilage Damage in the Adjuvant Arthritis Rat Model Through Regulation of the Indian Hedgehog Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ganggang Ma ◽  
Yang Yang ◽  
Yong Chen ◽  
Xin Wei ◽  
Jie Ding ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Signaling Pathway ◽  
Rat Model ◽  
Adjuvant Arthritis ◽  
Hedgehog Signaling ◽  
Cartilage Damage ◽  
Chondrocyte Apoptosis ◽  
Indian Hedgehog ◽  
Hedgehog Signaling Pathway ◽  
Articular Cartilage Damage

Articular cartilage damage with subsequent impairment of joint function is a common feature of articular diseases, in particular, rheumatoid arthritis and osteoarthritis. While articular cartilage injury mediated by chondrocyte apoptosis is a known major pathological feature of arthritis, the specific mechanisms remain unclear at present. Transient receptor potential melastatin-like seven channel (TRPM7) is reported to play an important regulatory role in apoptosis. This study focused on the effects of TRPM7 on arthritic chondrocyte injury and its underlying mechanisms of action. Sodium nitroprusside (SNP)-induced rat primary chondrocyte apoptosis and rat adjuvant arthritis (AA) were used as in vitro and in vivo models, respectively. Blockage of TRPM7 with 2-APB or specific siRNA resulted in increased chondrocyte viability and reduced toxicity of SNP. Moreover, treatment with 2-APB enhanced the Bcl-2/Bax ratio and reduced cleaved PARP and IL-6, MMP-13 and ADAMTS-5 expression in SNP-treated chondrocytes. Activation of Indian Hedgehog with purmorphamine reversed the protective effects of 2-APB on SNP-induced chondrocyte apoptosis. Blockage of TRPM7 with 2-APB relieved the clinical signs of AA in the rat model and reduced the arthritis score and paw swelling. Similar to findings in SNP-treated chondrocytes, 2-APB treatment increased the Bcl-2/Bax ratio and suppressed cleaved PARP, IL-6, MMP-13, ADAMTS-5, TRPM7, and Indian hedgehog expression in articular cartilage of AA rats. Our collective findings suggest that blockade of TRPM7 could effectively reduce chondrocyte apoptosis and articular cartilage damage in rats with adjuvant arthritis through regulation of the Indian Hedgehog signaling pathway.

scholarly journals HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Xiaodong Gu ◽  
Fei Li ◽  
Yangyang Gao ◽  
Xianda Che ◽  
Pengcui Li
Keyword(s):  
Articular Cartilage ◽  
Histone Deacetylase ◽  
Cartilage Damage ◽  
Adenovirus Vector ◽  
Cartilage Degeneration ◽  
Sprague Dawley ◽  
Chondrocyte Hypertrophy ◽  
Sprague Dawley Rats ◽  
Histone Deacetylase 4 ◽  
Safranin O

Abstract Background The aim of this study was to evaluate whether histone deacetylase 4 S246/467/632A mutant (m-HDAC4) has enhanced function at histone deacetylase 4 (HDAC4) to attenuate cartilage degeneration in a rat model of osteoarthritis (OA). Methods Chondrocytes were infected with Ad-m-HDAC4-GFP or Ad-HDAC4-GFP for 24 h, incubated with interleukin-1β (IL-1β 10 ng/mL) for 24 h, and then measured by RT-qPCR. Male Sprague-Dawley rats (n = 48) were randomly divided into four groups and transduced with different vectors: ACLT/Ad-GFP, ACLT/Ad-HDAC4-GFP, ACLT/Ad-m-HDAC4-GFP, and sham/Ad-GFP. All rats received intra-articular injections 48 h after the operation and every 3 weeks thereafter. Cartilage damage was assessed using radiography and Safranin O staining and quantified using the OARSI score. The hypertrophic and anabolic molecules were detected by immunohistochemistry and RT-qPCR. Results M-HDAC4 decreased the expression levels of Runx-2, Mmp-13, and Col 10a1, but increased the levels of Col 2a1 and ACAN more effectively than HDAC4 in the IL-1β-induced chondrocyte OA model; upregulation of HDAC4 and m-HDAC4 in the rat OA model suppressed Runx-2 and MMP-13 production, and enhanced Col 2a1 and ACAN synthesis. Stronger Safranin O staining was detected in rats treated with m-HDAC4 than in those treated with HDAC4. The resulting OARSI scores were lower in the Ad-m-HDAC4 group (5.80 ± 0.45) than in the Ad-HDAC4 group (9.67 ± 1.83, P = 0.045). The OARSI scores were highest in rat knees that underwent ACLT treated with Ad-GFP control adenovirus vector (14.93 ± 2.14, P = 0.019 compared with Ad-HDAC4 group; P = 0.003 compared with Ad-m-HDAC4 group). Lower Runx-2 and MMP-13 production, and stronger Col 2a1 and ACAN synthesis were detected in rats treated with m-HDAC4 than in those treated with HDAC4. Conclusions M-HDAC4 repressed chondrocyte hypertrophy and induced chondrocyte anabolism in the nucleus. M-HDAC4 was more effective in attenuating articular cartilage damage than HDAC4.

scholarly journals Baicalein Alleviates Osteoarthritis Progression in Mice by Protecting Subchondral Bone and Suppressing Chondrocyte Apoptosis Based on Network Pharmacology

2022 ◽  
Vol 12 ◽  
Author(s):  
Nanxing Yi ◽  
Yilin Mi ◽  
Xiaotong Xu ◽  
Naping Li ◽  
Fan Zeng ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Caspase 3 ◽  
Synovial Inflammation ◽  
Joint Disease ◽  
Network Pharmacology ◽  
Chondrocyte Apoptosis ◽  
Apoptotic Signaling

As life expectancy increases, Osteoarthritis (OA) is becoming a more frequently seen chronic joint disease. The main characteristics of OA are loss of articular cartilage, subchondral bone sclerosis, and synovial inflammation. Baicalein (Bai), a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been demonstrated to exert notable anti-inflammatory effects in previous studies, suggesting its potential effect in the treatment of OA. In this study, we first predicted the action targets of Bai, mapped target genes related to OA, identified potential anti-OA targets for Bai, performed gene ontology (GO) enrichment, and KEGG signaling pathway analyses of the action targets, and analyzed the molecular docking of key Bai targets. Additionally, the effect and potential mechanism of Bai against OA were verified in mouse knee OA models induced by destabilized medial meniscus (DMM) surgery. GO and KEGG analyses showed that 19 anti-OA targets were mainly involved in the response to oxidative stress, the response to hypoxia and apoptosis, and the PI3K-Akt and p53 signaling pathways. Molecular docking results indicated that BAX, BCL 2, and Caspase 3 enriched in the apoptotic signaling pathway have high binding affinity with Bai. Validation experiments showed that Bai can significantly attenuate the loss of articular cartilage (OARSI score), suppress synovial inflammation (synovitis score), and ameliorate subchondral bone resorption measured by micro-CT. In addition, Bai notably inhibited the expression of apoptosis-related proteins in articular cartilage (BAX, BCL 2, and Caspase 3). By combining network pharmacology with experimental validation, our study identifies and verifies the importance of the apoptotic signaling pathway in the treatment of OA by Bai. Bai may have promising application and potential therapeutic value in OA treatment.

Osteoblasts Regulate the Expression of ADAMTS and MMPs in Chondrocytes through ERK Signaling Pathway

2021 ◽  
Author(s):  
Xiao Ding ◽  
Wei Xiang ◽  
Defeng Meng ◽  
Wang Chao ◽  
Han Fei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Signaling Pathway ◽  
Subchondral Bone ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Blue Staining ◽  
Rt Pcr ◽  
Alizarin Red ◽  
Group I

Objective Degradative enzymes such as matrix metalloproteinase (MMP) and disintegrin metalloproteinase with platelet thrombin-sensitive protein-like motifs (ADAMTS) play a key role in the development of osteoarthritis (OA). We aimed to investigate the effects of OA subchondral osteoblasts on the expression of ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 in chondrocytes and the regulation of mitogen-activated protein kinase (MAPK) signaling pathway. Methods A rat knee OA model was constructed by cutting the anterior cruciate ligament of the knee joints, and normal rat articular cartilage chondrocytes (N-ACC), OA rat articular cartilage chondrocytes (O-ACC), normal subchondral bone osteoblasts (N-SBO), and OA subchondral bone osteoblasts (O-SBO) were isolated and extracted. The expressions of O-ACC and O-SBO COL1 and COL2 were detected respectively. Chondrocytes were identified by immunofluorescence of COL2 and toluidine blue staining, and osteoblasts were identified by COL1 immunofluorescence, alkaline phosphatase (ALP), and Alizarin Red staining. Gene expression of COL1, COL2, and aggrecan in normal chondrocytes and OA chondrocytes, and gene expression of osteoblast ALP and osteocalcin (OCN) were detected by RT-PCR to identify the two chondrocytes and the two osteoblast phenotypes. The constructing N-ACC group, O-ACC group, N-ACC + N-SBO group, N-ACC + O-SBO group, O-ACC + N-SBO group, O-ACC + O-SBO group, I + N-ACC + O-SBO group, and I + O-ACC + O-SBO group cell cultures, and the expression of ERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 genes in chondrocytes cultured for 0, 24, 48, and 72 h were detected by RT-PCR. The protein expressions of pERK, ADAMTS4, ADAMTS5, MMP-3, MMP-9, and MMP-13 were detected by Western blot. Results Conclusions

scholarly journals eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

2021 ◽  
Vol 22 (13) ◽  
pp. 6719
Author(s):  
Ashleigh M. Philp ◽  
Sam Butterworth ◽  
Edward T. Davis ◽  
Simon W. Jones
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Cytokines ◽  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Matrix Metalloproteases ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Pro Inflammatory Cytokines

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

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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