Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time‐based biomarkers: A feasibility study

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.

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Ultrashort echo time imaging of normal middle ear ossicles: a feasibility study

Dentomaxillofacial Radiology ◽

10.1259/dmfr/23423376 ◽

2012 ◽

Vol 41 (7) ◽

pp. 601-604 ◽

Cited By ~ 4

Author(s):

K Yamashita ◽

T Yoshiura ◽

A Hiwatashi ◽

H Kamano ◽

H Honda

Keyword(s):

Feasibility Study ◽

Middle Ear ◽

Ultrashort Echo Time ◽

Ear Ossicles ◽

Echo Time

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Detecting Articular Cartilage and Meniscus Deformation Effects Using Magnetization Transfer Ultrashort Echo Time (MT-UTE) Modeling during Mechanical Load Application: Ex Vivo Feasibility Study

Cartilage ◽

10.1177/1947603520976771 ◽

2020 ◽

pp. 194760352097677

Author(s):

Saeed Jerban ◽

Akhil Kasibhatla ◽

Yajun Ma ◽

Mei Wu ◽

Yanjun Chen ◽

...

Keyword(s):

Articular Cartilage ◽

Mechanical Load ◽

Ex Vivo ◽

Magnetization Transfer ◽

Knee Joints ◽

Loading Conditions ◽

Ultrashort Echo Time ◽

Short T2 ◽

Echo Time ◽

Magnetic Resonance Imaging Mri

Objective Ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences have improved imaging of short T2 musculoskeletal (MSK) tissues. UTE-MRI combined with magnetization transfer modeling (UTE-MT) has demonstrated robust assessment of MSK tissues. This study aimed to investigate the variation of UTE-MT measures under mechanical loading in tibiofemoral cartilage and meniscus of cadaveric knee joints. Design Fourteen knee joints from young ( n = 8, 42 ± 12 years old) and elderly ( n = 6, 89 ± 4 years old) donors were scanned on a 3-T scanner under 3 loading conditions: load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-MT sequences were performed at each loading condition. Macromolecular proton fraction (MMF) was calculated from UTE-MT modeling. Wilcoxon rank sum test was used to examine the MRI data differences between loading conditions. Results For young donors, MMF increased in all grouped regions of interest (meniscus [M], femoral articular cartilage [FAC], tibial articular cartilage [TAC], articular cartilage regions covered by meniscus [AC-MC], and articular cartilage regions uncovered by meniscus [AC-UC]) when the load increased from 300 to 500 N. The increases in MMF were significant for M (13.3%, P < 0.01) and AC-MC (9.2%, P = 0.04). MMF decreased in all studied regions after unloading, which was significant only for AC-MC (−8.9%, P = 0.01). For elderly donors, MRI parameters did not show significant changes by loading or unloading. Conclusion This study highlights the potential of the UTE-MT modeling combined with knee loading in differentiating between normal and abnormal knees. Average tissue deformation effects were likely higher and more uniformly distributed in the joints of young donors compared with elderly donors.

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