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BackgroundHealthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA). PurposeTo quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA. Study TypeRetrospective study. SubjectsFourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren‐Lawrence [KL] grade: 0; final KL grade: 3 over the 10‐year study). Field Strength/Sequence3.0‐T and 14.1‐T, biomechanics‐based displacement‐encoded imaging, fast spin echo, multi‐slice multi‐echoT2mapping. AssessmentWe studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades. Statistical TestsMultiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold atα = 0.05. ResultsGradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (R2 = 0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not. Data ConclusionSpatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early‐stage degeneration. Evidence Level1 Technical EfficacyStage 1
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Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis
ObjectiveTo elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (OA). MethodsThree‐month–old decorin‐null (Dcn−/−) and inducible decorin‐knockout (DcniKO) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post‐traumaticOA. TheOAphenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn−/−mice were stimulated with the inflammatory cytokine interleukin‐1β (IL‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response toIL‐1β and release ofsGAGs were quantified. ResultsIn both Dcn−/−and DcniKOmice, the absence of decorin resulted in acceleratedsGAGloss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P< 0.05). Also, Dcn−/−mice developed more salient osteophytes, illustrating more severeOA. In cartilage explants treated withIL‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion ofsGAGs was released to the media from Dcn−/−mouse explants, in both live and devitalized conditions (P< 0.05). ConclusionIn post‐traumaticOA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.
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- Award ID(s):
- 1662544
- PAR ID:
- 10456511
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Arthritis & Rheumatology
- Volume:
- 72
- Issue:
- 8
- ISSN:
- 2326-5191
- Format(s):
- Medium: X Size: p. 1266-1277
- Size(s):
- p. 1266-1277
- Sponsoring Org:
- National Science Foundation
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