scholarly journals Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors

1997 ◽  
Vol 323 (2) ◽  
pp. 483-488 ◽  
Author(s):  
Kevin M. BOTTOMLEY ◽  
Neera BORKAKOTI ◽  
David BRADSHAW ◽  
Paul A. BROWN ◽  
Michael J. BROADHURST ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cartilage Degradation ◽  
Cartilage Destruction ◽  
Collagen Degradation ◽  
Cartilage Explants ◽  
Nasal Cartilage ◽  
Sequence Production ◽  
C Terminus ◽  
Interleukin 1Α ◽  
Minor Sequence

N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin 1α revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin 1α. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r = 0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1α-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation.

Lipophilic statins prevent matrix metalloproteinase-mediated cartilage collagen breakdown by inhibiting protein geranylgeranylation

2010 ◽  
Vol 69 (12) ◽  
pp. 2189-2198 ◽  
Author(s):  
Matt J Barter ◽  
Wang Hui ◽  
Rachel L Lakey ◽  
John B Catterall ◽  
Tim E Cawston ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Gelatin Zymography ◽  
Cartilage Degradation ◽  
Collagen Degradation ◽  
Signalling Pathway ◽  
Oncostatin M ◽  
Human Articular Cartilage ◽  
Gelatinase Activity ◽  
Nasal Cartilage ◽  
Pathway Activation

ObjectiveTo investigate if statins prevent cartilage degradation and the production of collagenases and gelatinases in bovine nasal and human articular cartilage after proinflammatory cytokine stimulation.MethodsIn a cartilage degradation model, the effects of several statins were assessed by measuring proteoglycan degradation and collagen degradation, while collagenolytic and gelatinolytic activity in culture supernatants were determined by collagen bioassay and gelatin zymography. The production of matrix metalloproteinases (MMPs) in cartilage and chondrocytes were analysed by real-time reverse transcriptase PCR and immunoassay. Cytokine-induced signalling pathway activation was studied by immunoblotting.ResultsSimvastatin and mevastatin significantly inhibited interleukin 1 (IL-1)+oncostatin M (OSM)-induced collagen degradation; this was accompanied with a marked decrease in collagenase and gelatinase activity from bovine nasal cartilage. The cholesterol pathway intermediate mevalonic acid reversed the simvastatin-mediated protection of cartilage degradation, and the expression and production of collagenase (MMP-1 and MMP-13) and gelatinase (MMP-2 and MMP-9). Statins also significantly decreased MMP-1 and MMP-13 expression in human articular cartilage and chondrocytes stimulated with IL-1+OSM, and blocked the activation of critical proinflammatory signalling pathways required for MMP expression. The loss of the isoprenoid intermediate geranylgeranyl pyrophosphate due to statin treatment accounted for the inhibition of MMP expression and signalling pathway activation.ConclusionsThis study shows, for the first time, that lipophilic statins are able to block cartilage collagen breakdown induced by proinflammatory cytokines, by downregulating key cartilage-degrading enzymes. This demonstrates a possible therapeutic role for statins in acting as anti-inflammatory agents and in protecting cartilage from damage in joint diseases.

scholarly journals Glucosamine Hydrochloride but Not Chondroitin Sulfate Prevents Cartilage Degradation and Inflammation Induced by Interleukin-1α in Bovine Cartilage Explants

Cartilage ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Cécile Bascoul-Colombo ◽  
Iveta Garaiova ◽  
Sue F. Plummer ◽  
John L. Harwood ◽  
Bruce Caterson ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Cartilage Degradation ◽  
Cartilage Explants ◽  
Glucosamine Hydrochloride ◽  
Interleukin 1Α ◽  
Bovine Cartilage

scholarly journals Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model

2021 ◽  
Vol 22 (6) ◽  
pp. 2987
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Seong Jae Han ◽  
Seung Hee Yun ◽  
Seokjin Hwang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Medial Meniscus ◽  
Interleukin 1 ◽  
Bioactive Compound ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Cartilage Destruction ◽  
Raw 264.7 Cells ◽  
Potential Candidate ◽  
Cox 2

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1β)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1β-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.

Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes

2005 ◽  
Vol 24 (1) ◽  
pp. 63-70 ◽  
Author(s):  
M. Fichter ◽  
U. Körner ◽  
J. Schömburg ◽  
L. Jennings ◽  
A. A. Cole ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Articular Chondrocytes ◽  
Degradation Products ◽  
Collagen Degradation ◽  
Collagen Degradation Products

scholarly journals A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Louie C. Alexander ◽  
Grant McHorse ◽  
Janet L. Huebner ◽  
Anne-Christine Bay-Jensen ◽  
Morten A. Karsdal ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Joint Inflammation ◽  
Cartilage Degradation ◽  
Womac Pain ◽  
Type Iii Collagen ◽  
Type I ◽  
Radiographic Imaging ◽  
Type Iii

Abstract Objective To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Methods Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). Results BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. Conclusions To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

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