Document Type
Article
Publication Date
5-3-2025
Abstract
OBJECTIVE: This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.
METHODS: Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice underwent either DMM or sham surgery and were evaluated at 2 and 8 weeks postoperatively. Relative fluorescence intensity was quantified within the AC, CC and SB, complemented by micro-CT, safranin O staining, and collagen II immunohistochemistry staining.
RESULTS: The methodology successfully preserved sample integrity and original dye distribution. Fluorescent imaging revealed that small solute was mainly restricted by the tidemark, while large solute showed limited permeability in AC. Permeability of AC remained elevated in the DMM group at both time points. Increased permeability in CC and SB was observed only at 8 weeks post-DMM surgery, accompanied by reduced collagen II amount.
CONCLUSIONS: In live mice, the tidemark serves as a barrier to small molecule diffusion, while the cartilage surface restricts larger molecules; however, both structures exhibit increased permeability in OA. These findings advance the understanding of OA pathogenesis and suggest potential therapeutic targets related to cartilage permeability.
TRANSLATIONAL POTENTIAL: The findings of this study advance the understanding of osteoarthritis pathogenesis by elucidating the role of solute transport alterations in cartilage and subchondral bone, thereby suggesting potential therapeutic targets aimed at modulating cartilage permeability to improve joint health in osteoarthritis.
Recommended Citation
Chen, Mengcun; Yang, Yanmei; Cui, Mingshu; and Wang, Bin, "Solute Transport From Synovial Fluid to Articular Cartilage and Subchondral Bone at Different Stages of Osteoarthritis in a Live Mouse Model" (2025). Center for Translational Medicine Faculty Papers. Paper 130.
https://jdc.jefferson.edu/transmedfp/130
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
40421143
Language
English
Comments
This article is the author’s final published version in the Journal of Orthopaedic Translation, Volume 52, May 2025, Pages 291-300.
The published version is available at https://doi.org/10.1016/j.jot.2025.04.012. Copyright © 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society.