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1. Non-Destructive Spatial Mapping of Glycosaminoglycan Loss in Native and Degraded Articular Cartilage Using Confocal Raman Microspectroscopy

   https://doi.org/10.3389/fbioe.2021.744197  

   Gao, Tianyu; Boys, Alexander J.; Zhao, Crystal; Chan, Kiara; Estroff, Lara A.; Bonassar, Lawrence J. (October 2021, Frontiers in Bioengineering and Biotechnology)

   Articular cartilage is a collagen-rich tissue that provides a smooth, lubricated surface for joints and is also responsible for load bearing during movements. The major components of cartilage are water, collagen, and proteoglycans. Osteoarthritis is a degenerative disease of articular cartilage, in which an early-stage indicator is the loss of proteoglycans from the collagen matrix. In this study, confocal Raman microspectroscopy was applied to study the degradation of articular cartilage, specifically focused on spatially mapping the loss of glycosaminoglycans (GAGs). Trypsin digestion was used as a model for cartilage degradation. Two different scanning geometries for confocal Raman mapping, cross-sectional and depth scans, were applied. The chondroitin sulfate coefficient maps derived from Raman spectra provide spatial distributions similar to histological staining for glycosaminoglycans. The depth scans, during which subsurface data were collected without sectioning the samples, can also generate spectra and GAG distributions consistent with Raman scans of the surface-to-bone cross sections. In native tissue, both scanning geometries demonstrated higher GAG content at the deeper zone beneath the articular surface and negligible GAG content after trypsin degradation. On partially digested samples, both scanning geometries detected an ∼100 μm layer of GAG depletion. Overall, this research provides a technique with high spatial resolution (25 μm pixel size) to measure cartilage degradation without tissue sections using confocal Raman microspectroscopy, laying a foundation for potential in vivo measurements and osteoarthritis diagnosis. 

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2. Variation in Articular Cartilage Thickness Among Extant Salamanders and Implications for Limb Function in Stem Tetrapods

   https://doi.org/10.3389/fevo.2021.671006  

   Molnar, Julia L. (May 2021, Frontiers in Ecology and Evolution)

   The size and shape of articular cartilage in the limbs of extant vertebrates are highly variable, yet they are critical for understanding joint and limb function in an evolutionary context. For example, inferences about unpreserved articular cartilage in early tetrapods have implications for how limb length, joint range of motion, and muscle leverage changed over the tetrapod water-land transition. Extant salamanders, which are often used as functional models for early limbed vertebrates, have much thicker articular cartilage than most vertebrate groups, but the exact proportion of cartilage and how it varies across salamander species is unknown. I aimed to quantify this variation in a sample of 13 salamanders representing a broad range of sizes, modes of life, and genera. Using contrast-enhanced micro-CT, cartilage dimensions and bone length were measured non-destructively in the humerus, radius, ulna, femur, tibia, and fibula of each specimen. Cartilage correction factors were calculated as the combined thickness of the proximal and distal cartilages divided by the length of the bony shaft. Articular cartilage added about 30% to the length of the long bones on average. Cartilage was significantly thicker in aquatic salamanders (42 ± 14% in the humerus and 35 ± 8 in the femur) than in terrestrial salamanders (21 ± 7% in both humerus and femur). There was no consistent relationship between relative cartilage thickness and body size or phylogenetic relatedness. In addition to contributing to limb length, cartilage caps increased the width and breadth of the epiphyses by amounts that varied widely across taxa. To predict the effect of salamander-like cartilage correction factors on muscle leverage, a simplified model of the hindlimb of the Devonian stem tetrapod Acanthostega was built. In this model, the lever arms of muscles that cross the hip at an oblique angle to the femur was increased by up to six centimeters. Future reconstructions of osteological range of motion and muscle leverage in stem tetrapods and stem amphibians can be made more rigorous by explicitly considering the possible effects of unpreserved cartilage and justifying assumptions based on available data from extant taxa, including aquatic and terrestrial salamanders. 

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3. Effect of Whole Body Parameters on Knee Joint Biomechanics: Implications for ACL Injury Prevention During Single-Leg Landings

   https://doi.org/10.1177/03635465231174899  

   Sadeqi, Sara; Norte, Grant E; Murray, Amanda; Erbulut, Deniz U; Goel, Vijay K (July 2023, The American Journal of Sports Medicine)

   Background:Previous studies have examined the effect of whole body (WB) parameters on anterior cruciate ligament (ACL) strain and loads, as well as knee joint kinetics and kinematics. However, articular cartilage damage occurs in relation to ACL failure, and the effect of WB parameters on ACL strain and articular cartilage biomechanics during dynamic tasks is unclear. Purposes:(1) To investigate the effect of WB parameters on ACL strain, as well as articular cartilage stress and contact force, during a single-leg cross drop (SLCD) and single-leg drop (SLD). (2) To identify WB parameters predictive of high ACL strain during these tasks. Study Design:Descriptive laboratory study. Methods:Three-dimensional motion analysis data from 14 physically active men and women were recorded during an SLCD and SLD. OpenSim was used to obtain their kinematics, kinetics, and muscle forces for the WB model. Using these data in kinetically driven finite element simulations of the knee joint produced outputs of ACL strains and articular cartilage stresses and contact forces. Spearman correlation coefficients were used to assess relationships between WB parameters and ACL strain and cartilage biomechanics. Moreover, receiver operating characteristic curve analyses and multivariate binary logistic regressions were used to find the WB parameters that could discriminate high from low ACL strain trials. Results:Correlations showed that more lumbar rotation away from the stance limb at peak ACL strain had the strongest overall association (ρ = 0.877) with peak ACL strain. Higher knee anterior shear force (ρ = 0.895) and lower gluteus maximus muscle force (ρ = 0.89) at peak ACL strain demonstrated the strongest associations with peak articular cartilage stress or contact force in ≥1 of the analyzed tasks. The regression model that used muscle forces to predict high ACL strain trials during the dominant limb SLD yielded the highest accuracy (93.5%), sensitivity (0.881), and specificity (0.952) among all regression models. Conclusion:WB parameters that were most consistently associated with and predictive of high ACL strain and poor articular cartilage biomechanics during the SLCD and SLD tasks included greater knee abduction angle at initial contact and higher anterior shear force at peak ACL strain, as well as lower gracilis, gluteus maximus, and medial gastrocnemius muscle forces. Clinical relevance:Knowledge of which landing postures create a high risk for ACL or cartilage injury may help reduce injuries in athletes by avoiding those postures and practicing the tasks with reduced high-risk motions, as well as by strengthening the muscles that protect the knee during single-leg landings. 

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4. Quantification of Cartilage Poroelastic Material Properties Via Analysis of Loading-Induced Cell Death

   https://doi.org/10.1115/1.4065194  

   Kotelsky, Alexander; Carrier, Joseph S; Buckley, Mark R (August 2024, Journal of Biomechanical Engineering)

   Abstract Articular cartilage (AC) is a load-bearing tissue that covers long bones in synovial joints. The biphasic/poroelastic mechanical properties of AC help it to protect joints by distributing loads, absorbing impact forces, and reducing friction. Unfortunately, alterations in these mechanical properties adversely impact cartilage function and precede joint degeneration in the form of osteoarthritis (OA). Thus, understanding what factors regulate the poroelastic mechanical properties of cartilage is of great scientific and clinical interest. Transgenic mouse models provide a valuable platform to delineate how specific genes contribute to cartilage mechanical properties. However, the poroelastic mechanical properties of murine articular cartilage are challenging to measure due to its small size (thickness ∼ 50 microns). In the current study, our objective was to test whether the poroelastic mechanical properties of murine articular cartilage can be determined based solely on time-dependent cell death measurements under constant loading conditions. We hypothesized that in murine articular cartilage subjected to constant, sub-impact loading from an incongruent surface, cell death area and tissue strain are closely correlated. We further hypothesized that the relationship between cell death area and tissue strain can be used—in combination with inverse finite element modeling—to compute poroelastic mechanical properties. To test these hypotheses, murine cartilage-on-bone explants from different anatomical locations were subjected to constant loading conditions by an incongruent surface in a custom device. Cell death area increased over time and scaled linearly with strain, which rose in magnitude over time due to poroelastic creep. Thus, we were able to infer tissue strain from cell death area measurements. Moreover, using tissue strain values inferred from cell death area measurements, we applied an inverse finite element modeling procedure to compute poroelastic material properties and acquired data consistent with previous studies. Collectively, our findings demonstrate in the key role poroelastic creep plays in mediating cell survival in mechanically loaded cartilage and verify that cell death area can be used as a surrogate measure of tissue strain that enables determination of murine cartilage mechanical properties. 

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5. Timing of cartilage articulation following impact injury affects the response of surface zone chondrocytes

   https://doi.org/10.1002/jor.26002  

   Thompson, Caroline L; Bonassar, Lawrence J (February 2025, Journal of Orthopaedic Research)

   Abstract Post‐traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring‐loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain‐dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early‐stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate. 

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