An official website of the United States government
ABSTRACT The articular cartilage extracellular matrix (ECM) is a complex network of biomolecules that includes fibronectin (FN). FN acts as an extracellular glue, controlling the assembly of other macromolecular constituents to the ECM. However, how FN participates in the binding and retention of synovial fluid components, the natural lubricant of articulated joints, to form a wear-protecting and lubricating film has not been established. This study reports on the role of FN and its molecular conformation in mediating macromolecular assembly of synovial fluid ad-layers. FN films as precursor films on functionalized surfaces, a model of FN’s articular cartilage surface, adsorbed and retained different amounts of synovial fluid (SF). FN conformational changes were induced by depositing FN at pH 7 (extended state) or at pH 4 (unfolded state) on self-assembled monolayers on gold-coated quartz crystals, followed by adsorption of diluted SF (25%) onto FN precursor films. Mass density, thin film compliance, surface morphologies, and adsorbed FN films’ secondary and tertiary structures reveal pH-induced differences. FN films deposited at pH 4 were thicker, more rigid, showed a more homogeneous morphology, and had alteredα-helix andβ-sheet content, compared to FN films deposited at pH 7. FN precursor films deposited at pH 7 adsorbed and retained more synovial fluid than those at pH 4, revealing the importance of FN conformation at the articular cartilage surface to bind and maintain a thin lubricating and wear protective layer of synovial fluid constituents. This knowledge will enable a better understanding of the molecular regulation of articular cartilage-SF interface homeostasis and joint pathophysiology and identify molecular interactions and synergies between the articular cartilage ECM and SF to reveal the complexity of joint biotribology.
more »
« less
Shining a light on the tribological rehydration of cartilage.
Cartilage exudes interstitial fluid and metabolic waste products during loading and recovers interstitial fluid and nutrients from the synovial fluid during articulation through mechanisms that remain unclear. Here, Moore et al illustrating a fundamentally new and unanticipated mechanism of fluid and nutrient uptake by articular cartilage. The results suggest that fluid entrained at the leading edge of contact is pressurized and subsequently forced back into the porous articular surface to restore hydration, thickness, nutrition and lubrication.
more »
« less
- Award ID(s):
- 1635536
- PAR ID:
- 10183010
- Date Published:
- Journal Name:
- Tribology lubrication technology
- Volume:
- 73
- Issue:
- 8
- ISSN:
- 1545-858X
- Page Range / eLocation ID:
- 51
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Recreating articular cartilage tri-layered patterning for an engineered in vitro cell construct holds promise for advancing cartilage repair efforts. Our approach involves the development of a mul-tichambered perfusion tissue bioreactor that regulates fluid shear stress levels similar to the gradated hydrodynamic environment in articular cartilage. COMSOL modeling reveals our ta-pered cell chamber design will produce three different shear levels, high in the 22 – 41 mPa range, medium in the 4.5 – 8.4 mPa range, and low in the 2.2 – 3.8 mPa range and distributed across the surface of our mesenchymal stromal cell (MSC) encapsulated construct. In a 14-day bioreactor culture, we assess how fluid shear magnitude and cell vertical location within a 3D construct influence cell chondrogenesis. Notably, Sox9 expression for MSCs cultivated in our reactor shows spatially patterned gene upregulations coding for key chondrogenic marker pro-teins. Beginning with the high shear stress region, lubricin and type II collagen gene increases of 410 and 370-fold indicate cell movement towards a superficial zone architype which is further supported by histological and immunohistochemical stains illustrating the formation of a dense proteoglycan matrix enriched with lubricin, versican, and collagen types I and II molecules. For the medium shear stress region high aggrecan and type II collagen gene expressions of 2.3 and 400-fold, respectively, along with high proteoglycan analyses show movement toward a superfi-cial/mid-zone cartilage architype. For low shear stress regions higher collagen types II and X gene upregulations of 550 and 8,300-fold, the latter being 2x of that for the high shear regime, indicate cell movement with deep zone characteristics. Collectively, biochemical analysis, histol-ogy, and gene expression data demonstrated that our fluid shear bioreactor induced a stratified structure within tissue engineered constructs, demonstrating the feasibility of using this ap-proach to recapitulate the structure of native articular cartilage.more » « less
-
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.more » « less
-
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.more » « less
-
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.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- The DOI is not currently available.
