Physical Diagnostics of Cartilage Degeneration

Treppo, S.; Berkenblit, Scott I.; Bombard, David L.; Frank, Eliot H.; Grodzinsky, Alan J.

doi:10.1007/978-4-431-68497-8_5

Cited by 3 publications

(8 citation statements)

References 70 publications

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“…For the less severe, more physiological-like MMP-13 digestion, immunohistochemistry of untreated and MMP-13 treated cartilage disks using monoclonal neo-epitope antibody 9A4 to reveal collagenase cleavage of collagen showed that 24 h MMP-13 treatment introduced partial degradation of the collagen network in the upper 30 μm of the superficial zone (Figure S2). As a result, the maximum adhesion force, F ad , between aggrecan and collagen significantly increased by a factor of ≈2.5× for both MMP-13 and BC treatments at the same indentation depth (≈500 nm) and t d = 30 s in PBS (Figure a, Mann–Whitney test, p < 0.001). The total adhesion energy, E ad , also increased substantially for both treatments, where the BC treatment (≈3× increase) had even greater effects than the MMP-13 treatment (≈1.5× increase; Figure b, Mann–Whitney test, p < 0.001).…”

Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

“…The presence of nondegraded collagen is further supported by the absence of collagenase cleavage sites in the superficial zone, which can be detected via immunohistochemistry (Figure S2). 37 The fibrillar collagen network is expected to be the major constituent of the trypsin-treated disks, as the physically adsorbed surface-active phospholipid layer 39−41 is expected to be removed via rinsing in PBS, 47 and proteoglycans such as aggrecan and lubricin were removed by trypsin digestion (Figure 7). While some hyaluronan may remain on the surface, recent studies on cartilage surface lubrication have shown that a 12 h incubation with trypsin likely removed most hyaluronan constituents 48 due to the loss of its anchorage with aggrecan 7 and lubricin.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Human recombinant matrix metalloprotease-13 (MMP-13) is a typical enzyme up-regulated in osteoarthritic cartilage, which contributes to the collagen fibril degradation in vivo . A previous immunohistochemistry study showed that 24 h MMP-13 digestion introduces partial defibrillization of collagen within the top ≈30 μm surface of cartilage (Figure S2), although these changes are not visible at the microscale via SEM imaging (Figure ). As a result, we observed an ≈2.5× increase in F ad and an ≈1.5× increase in E ad (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…(2) Figure S2: Immunohistochemistry of the untreated and MMP-13 digested cartilage disks. 37 (3) Figure S3: Amino acid sequence of calf type II collagen (colIIα1). 62 This material is available free of charge via the Internet at .…”

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Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

Rojas¹,

Batista²,

Lindburg

et al. 2014

Biomacromolecules

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In this study, we investigated the molecular adhesion between the major constituents of cartilage extracellular matrix, namely, the highly negatively charged proteoglycan aggrecan and the type II/IX/XI fibrillar collagen network, in simulated physiological conditions. Colloidal force spectroscopy was applied to measure the maximum adhesion force and total adhesion energy between aggrecan end-attached spherical tips (end radius R ≈ 2.5 μm) and trypsin-treated cartilage disks with undamaged collagen networks. Studies were carried out in various aqueous solutions to reveal the physical factors that govern aggrecan–collagen adhesion. Increasing both ionic strength and [Ca2+] significantly increased adhesion, highlighting the importance of electrostatic repulsion and Ca2+-mediated ion bridging effects. In addition, we probed how partial enzymatic degradation of the collagen network, which simulates osteoarthritic conditions, affects the aggrecan–collagen interactions. Interestingly, we found a significant increase in aggrecan–collagen adhesion even when there were no detectable changes at the macro- or microscales. It is hypothesized that the aggrecan–collagen adhesion, together with aggrecan–aggrecan self-adhesion, works synergistically to determine the local molecular deformability and energy dissipation of the cartilage matrix, in turn, affecting its macroscopic tissue properties.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

Rojas¹,

Batista²,

Lindburg

et al. 2014

Biomacromolecules

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Machine learning-based bioimpedance assessment of knee osteoarthritis severity

Muñoz,

Mosquera,

Rengifo

et al. 2024

Biomed. Phys. Eng. Express

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This study proposes a multiclass model to classify the severity of knee osteoarthritis (KOA) using bioimpedance measurements. The experimental setup considered three types of measurements using eight electrodes: global impedance with adjacent pattern, global impedance with opposite pattern, and direct impedance measurement, which were taken using an electronic device proposed by authors and based on the Analog Devices AD5933 impedance converter. The study comprised 37 participants, 25 with healthy knees and 13 with three different degrees of KOA. All participants performed 20 repetitions of each of the following five tasks: (i) sitting withthe knee bent, (ii) sitting with the knee extended, (iii) sitting and performing successive extensions and flexions of the knee, (iv) standing, and (v) walking. Data from the 15 experimental setups (3 types of measurements × 5 exercises) were used to train a multiclass random forest. The training and validation cycle was repeated 100 times using random undersampling. At each of the 100 cycles, 80% of the data were used for training and the rest for testing. The results showed that the proposed approach achieved average sensitivities and specificities of 100% for the four KAO severity grades in the extensión, cyclic, and gait tasks. This suggests that the proposed method can serve as a screening tool to determine which individuals should undergo X-rays or magnetic resonance imaging for further evaluation of KOA.

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Mechanical Testing of Cell-Material Constructs: A Review

Kisiday

Kerin

Grodzinsky

Biopolymer Methods in Tissue Engineering

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Physical Diagnostics of Cartilage Degeneration

Cited by 3 publications

References 70 publications

Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

Machine learning-based bioimpedance assessment of knee osteoarthritis severity

Mechanical Testing of Cell-Material Constructs: A Review

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