Mechanobiological model for simulation of injured cartilage degradation via proinflammatory cytokines and mechanical
(2020) In PLoS Computational Biology 16(6).- Abstract
Post-traumatic osteoarthritis (PTOA) is associated with cartilage degradation, ultimately leading to disability and decrease of quality of life. Two key mechanisms have been suggested to occur in PTOA: Tissue inflammation and abnormal biomechanical loading. Both mechanisms have been suggested to result in loss of cartilage proteoglycans, the source of tissue fixed charge density (FCD). In order to predict the simultaneous effect of these degrading mechanisms on FCD content, a computational model has been developed. We simulated spatial and temporal changes of FCD content in injured cartilage using a novel finite element model that incorporates (1) diffusion of the pro-inflammatory cytokine interleukin-1 into tissue, and (2) the effect... (More)
Post-traumatic osteoarthritis (PTOA) is associated with cartilage degradation, ultimately leading to disability and decrease of quality of life. Two key mechanisms have been suggested to occur in PTOA: Tissue inflammation and abnormal biomechanical loading. Both mechanisms have been suggested to result in loss of cartilage proteoglycans, the source of tissue fixed charge density (FCD). In order to predict the simultaneous effect of these degrading mechanisms on FCD content, a computational model has been developed. We simulated spatial and temporal changes of FCD content in injured cartilage using a novel finite element model that incorporates (1) diffusion of the pro-inflammatory cytokine interleukin-1 into tissue, and (2) the effect of excessive levels of shear strain near chondral defects during physiologically relevant loading. Cytokine-induced biochemical cartilage explant degradation occurs near the sides, top, and lesion, consistent with the literature. In turn, biomechanically-driven FCD loss is predicted near the lesion, in accordance with experimental findings: Regions near lesions showed significantly more FCD depletion compared to regions away from lesions (p<0.01). Combined biochemical and biomechanical degradation is found near the free surfaces and especially near the lesion, and the corresponding bulk FCD loss agrees with experiments. We suggest that the presence of lesions plays a role in cytokine diffusion-driven degradation, and also predisposes cartilage for further biomechanical degradation. Models considering both these cartilage degradation pathways concomitantly are promising in silico tools for predicting disease progression, recognizing lesions at high risk, simulating treatments, and ultimately optimizing treatments to postpone the development of PTOA.
(Less)
- author
- Eskelinen, Atte S.A. ; Tanska, Petri ; Florea, Cristina ; Orozco, Gustavo A. LU ; Julkunen, Petro ; Grodzinsky, Alan J. LU and Korhonen, Rami K.
- publishing date
- 2020-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Computational Biology
- volume
- 16
- issue
- 6
- article number
- e1007998
- pages
- 25 pages
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:32584809
- scopus:85087956774
- ISSN
- 1553-734X
- DOI
- 10.1371/journal.pcbi.1007998
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2020 Eskelinen et al.
- id
- 1e28751d-7904-477a-b5f8-bc2705e8b9bc
- date added to LUP
- 2022-06-08 11:45:33
- date last changed
- 2024-06-14 16:33:40
@article{1e28751d-7904-477a-b5f8-bc2705e8b9bc,
abstract = {{<p>Post-traumatic osteoarthritis (PTOA) is associated with cartilage degradation, ultimately leading to disability and decrease of quality of life. Two key mechanisms have been suggested to occur in PTOA: Tissue inflammation and abnormal biomechanical loading. Both mechanisms have been suggested to result in loss of cartilage proteoglycans, the source of tissue fixed charge density (FCD). In order to predict the simultaneous effect of these degrading mechanisms on FCD content, a computational model has been developed. We simulated spatial and temporal changes of FCD content in injured cartilage using a novel finite element model that incorporates (1) diffusion of the pro-inflammatory cytokine interleukin-1 into tissue, and (2) the effect of excessive levels of shear strain near chondral defects during physiologically relevant loading. Cytokine-induced biochemical cartilage explant degradation occurs near the sides, top, and lesion, consistent with the literature. In turn, biomechanically-driven FCD loss is predicted near the lesion, in accordance with experimental findings: Regions near lesions showed significantly more FCD depletion compared to regions away from lesions (p<0.01). Combined biochemical and biomechanical degradation is found near the free surfaces and especially near the lesion, and the corresponding bulk FCD loss agrees with experiments. We suggest that the presence of lesions plays a role in cytokine diffusion-driven degradation, and also predisposes cartilage for further biomechanical degradation. Models considering both these cartilage degradation pathways concomitantly are promising in silico tools for predicting disease progression, recognizing lesions at high risk, simulating treatments, and ultimately optimizing treatments to postpone the development of PTOA. </p>}},
author = {{Eskelinen, Atte S.A. and Tanska, Petri and Florea, Cristina and Orozco, Gustavo A. and Julkunen, Petro and Grodzinsky, Alan J. and Korhonen, Rami K.}},
issn = {{1553-734X}},
language = {{eng}},
number = {{6}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Computational Biology}},
title = {{Mechanobiological model for simulation of injured cartilage degradation via proinflammatory cytokines and mechanical}},
url = {{http://dx.doi.org/10.1371/journal.pcbi.1007998}},
doi = {{10.1371/journal.pcbi.1007998}},
volume = {{16}},
year = {{2020}},
}