scholarly journals The Anti-ADAMTS-5 Nanobody® M6495 Protects Cartilage Degradation Ex Vivo

2020 ◽  
Vol 21 (17) ◽  
pp. 5992
Author(s):  
Anne Sofie Siebuhr ◽  
Daniela Werkmann ◽  
Anne-C. Bay-Jensen ◽  
Christian S. Thudium ◽  
Morten Asser Karsdal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Type Ii Collagen ◽  
Cartilage Degradation ◽  
Collagen Degradation ◽  
Oncostatin M ◽  
Protective Effects ◽  
Type Ii ◽  
Healthy Cartilage ◽  
Bovine Cartilage ◽  
Cartilage Turnover

Osteoarthritis (OA) is associated with cartilage breakdown, brought about by ADAMTS-5 mediated aggrecan degradation followed by MMP-derived aggrecan and type II collagen degradation. We investigated a novel anti-ADAMTS-5 inhibiting Nanobody® (M6495) on cartilage turnover ex vivo. Bovine cartilage (BEX, n = 4), human osteoarthritic - (HEX, n = 8) and healthy—cartilage (hHEX, n = 1) explants and bovine synovium and cartilage were cultured up to 21 days in medium alone (w/o), with pro-inflammatory cytokines (oncostatin M (10 ng/mL) + TNFα (20 ng/mL) (O + T), IL-1α (10 ng/mL) or oncostatin M (50 ng/mL) + IL-1β (10 ng/mL)) with or without M6495 (1000−0.46 nM). Cartilage turnover was assessed in conditioned medium by GAG (glycosaminoglycan) and biomarkers of ADAMTS-5 driven aggrecan degradation (huARGS and exAGNxI) and type II collagen degradation (C2M) and formation (PRO-C2). HuARGS, exAGNxI and GAG peaked within the first culture week in pro-inflammatory stimulated explants. C2M peaked from day 14 by O + T and day 21 in co-culture experiments. M6495 dose dependently decreased huARGS, exAGNxI and GAG after pro-inflammatory stimulation. In HEX C2M was dose-dependently reduced by M6495. M6495 showed no effect on PRO-C2. M6495 showed cartilage protective effects by dose-dependently inhibiting ADAMTS-5 mediated cartilage degradation and inhibiting overall cartilage deterioration in ex vivo cartilage cultures.

A novel serological pharmacodynamic biomarker assessing type II collagen degradation in osteoarthritis patients

2021 ◽  
Vol 29 ◽  
pp. S91
Author(s):  
S.S Groen ◽  
D. Sinkeviciute ◽  
C.S. Thudium ◽  
P. Önnerfjord ◽  
M. Karsdal ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Collagen Degradation ◽  
Type Ii

scholarly journals One-year increase of Coll 2-1, a new marker of type II collagen degradation, in urine is highly predictive of radiological OA progression

2005 ◽  
Vol 13 (12) ◽  
pp. 1059-1065 ◽  
Author(s):  
M.A. Deberg ◽  
A.H. Labasse ◽  
J. Collette ◽  
L. Seidel ◽  
J.-Y. Reginster ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Collagen Degradation ◽  
Type Ii ◽  
One Year

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 The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation

2008 ◽  
Vol 16 (10) ◽  
pp. 1183-1191 ◽  
Author(s):  
N. Charni-Ben Tabassi ◽  
S. Desmarais ◽  
A.-C. Bay-Jensen ◽  
J.M. Delaissé ◽  
M.D. Percival ◽  
...  
Keyword(s):  
Type Ii Collagen ◽  
Collagen Degradation ◽  
Type Ii ◽  
Human Cartilage ◽  
Enzymatic Pathways
Sign in / Sign up

Export Citation Format

Share Document