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Articular surface integrity assessed by ultrasound is associated with biological characteristics of articular cartilage in early-stage degeneration.

ABSTRACT: Early diagnosis of articular cartilage damage and repeated evaluation of treatment efficacy are essential for osteoarthritis treatment. In this study, we established a simple ultrasound grading system for early degenerative articular cartilage and investigated its relationship with cartilage biological characteristics. The ultrasound grading system were based on surface integrity (S1a: continuous high-echo lines, S1b: discontinuous or weak high-echo lines, S2: surface irregular) and cartilage echogenicity (E1: with > 50%, E2: < 50% hypoechoic area of total cartilage layer) and verified by surface roughness (Ra; μm) and histological staining. Ra was lower in S1 than in S2, and the percentage of hypoechoic and safranin O-stained areas was positively correlated. Then we examined its relationship with histopathological evaluation (OARSI grade), gene expression, and protein production in responded to pro-inflammatory cytokine (IL-1ß) stimulation. OARSI grades were different among S grades. The superficial layer of S1 had higher expression of Collagen10, aggrecan, Sox9, and lower expression of Collagen1 and BMP2 than that of S2. S1 responded more pronouncedly to IL-1ß in IL-6, IL-8, and CCL2 production than S2. There was no difference among the E-grades. Taken together, our findings indicate that ultrasound assessment using surface integrity can reflect the biological characteristics of early degenerative articular cartilage.

SUBMITTER: Shi W

PROVIDER: S-EPMC9279397 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Articular surface integrity assessed by ultrasound is associated with biological characteristics of articular cartilage in early-stage degeneration.

Shi Wen W Kanamoto Takashi T Aihara Masaharu M Oka Shiro S Kuroda Sanae S Nakai Tsuyoshi T Mazuka Takeo T Takenaka Keisuke K Sato Yuji Y Tsukamoto Masahiro M Ebina Kosuke K Nakata Ken K

Scientific reports 20220713 1

Early diagnosis of articular cartilage damage and repeated evaluation of treatment efficacy are essential for osteoarthritis treatment. In this study, we established a simple ultrasound grading system for early degenerative articular cartilage and investigated its relationship with cartilage biological characteristics. The ultrasound grading system were based on surface integrity (S1a: continuous high-echo lines, S1b: discontinuous or weak high-echo lines, S2: surface irregular) and cartilage ec ...[more]

PMID: 35831407

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Project description:Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage.Key messagesAdenosine receptor A3 (A3) knockout results in progressive loss of articular cartilage in vivo. Ablation of A3 results in activation of matrix degradation and cartilage hypertrophy. A3 agonists downregulate RUNX2 and CaMKII expression in osteoarthritic human articular chondrocytes. A3 prevents articular cartilage matrix degradation induced by inflammation and osmotic fluctuations. A3 agonist inhibits proteolytic activity of cartilage-degrading enzymes.

Project description:An exact understanding of the interplay between the articulating tissues of the knee joint in relation to the osteoarthritis (OA)-related degeneration process is of considerable interest. Therefore, the aim of the present study was to characterize the biomechanical properties of mildly and severely degenerated human knee joints, including their menisci and tibial and femoral articular cartilage (AC) surfaces. A spatial biomechanical mapping of the articulating knee joint surfaces of 12 mildly and 12 severely degenerated human cadaveric knee joints was assessed using a multiaxial mechanical testing machine. To do so, indentation stress relaxation tests were combined with thickness and water content measurements at the lateral and medial menisci and the AC of the tibial plateau and femoral condyles to calculate the instantaneous modulus (IM), relaxation modulus, relaxation percentage, maximum applied force during the indentation, and the water content. With progressing joint degeneration, we found an increase in the lateral and the medial meniscal instantaneous moduli (p < 0.02), relaxation moduli (p < 0.01), and maximum applied forces (p < 0.01), while for the underlying tibial AC, the IM (p = 0.01) and maximum applied force (p < 0.01) decreased only at the medial compartment. Degeneration had no influence on the relaxation percentage of the soft tissues. While the water content of the menisci did not change with progressing degeneration, the severely degenerated tibial AC contained more water (p < 0.04) compared to the mildly degenerated tibial cartilage. The results of this study indicate that degeneration-related (bio-)mechanical changes seem likely to be first detectable in the menisci before the articular knee joint cartilage is affected. Should these findings be further reinforced by structural and imaging analyses, the treatment and diagnostic paradigms of OA might be modified, focusing on the early detection of meniscal degeneration and its respective treatment, with the final aim to delay osteoarthritis onset.

Dataset Information

Articular surface integrity assessed by ultrasound is associated with biological characteristics of articular cartilage in early-stage degeneration.

Publications

Articular surface integrity assessed by ultrasound is associated with biological characteristics of articular cartilage in early-stage degeneration.

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