Disuse atrophy of articular cartilage can be restored by mechanical reloading in mice.

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  • Additional Information
    • Source:
      Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: Dordrecht, Boston, Reidel.
    • Subject Terms:
      Cartilage, Articular*/pathology ; Cartilage, Articular*/metabolism ; Chondrocytes*/metabolism ; Chondrocytes*/pathology ; ADAMTS5 Protein*/metabolism ; ADAMTS5 Protein*/genetics ; Hindlimb Suspension*/adverse effects ; Stress, Mechanical*; Animals ; Mice ; Matrix Metalloproteinase 13/metabolism ; SOX9 Transcription Factor/metabolism ; SOX9 Transcription Factor/genetics ; Aggrecans/metabolism ; Collagen Type II/metabolism ; Male ; X-Ray Microtomography ; Weight-Bearing/physiology ; Atrophy ; Knee Joint/pathology ; Knee Joint/physiopathology ; Knee Joint/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Physical Conditioning, Animal
    • Abstract:
      Background: Moderate mechanical stress generated by normal joint loading and movements helps maintain the health of articular cartilage. Despite growing interest in the pathogenesis of cartilage degeneration caused by reduced mechanical stress, its reversibility by mechanical reloading is less understood. This study aimed to investigate the response of articular cartilage exposed to mechanical reloading after unloading in vivo and in vitro.
      Methods and Results: Disuse atrophy was induced in the knee joint cartilage of adult mice through hindlimb unloading by tail suspension. For in vivo experiments, mice were subjected to reloading with or without daily exercise intervention or surgical destabilization of the knee joint. Microcomputed tomography and histomorphometric analyses were performed on the harvested knee joints. Matrix loss and thinning of articular cartilage due to unloading were fully or partially restored by reloading, and exercise intervention enhanced the restoration. Subchondral bone density decreased by unloading and increased to above-normal levels by reloading. The severity of cartilage damage caused by joint instability was not different even with prior non-weight bearing. For in vitro experiments, articular chondrocytes isolated from the healthy or unloaded joints of the mice were embedded in agarose gel. After dynamic compression loading, the expression levels of anabolic (Sox9, Col2a1, and Acan) and catabolic (Mmp13 and Adamts5) factors of cartilage were analyzed. In chondrocytes isolated from the unloaded joints, similar to those from healthy joints, dynamic compression increased the expression of anabolic factors but suppressed the expression of catabolic factors.
      Conclusion: The results of this study indicate that the morphological changes in articular cartilage exposed to mechanical unloading may be restored in response to mechanical reloading by shifting extracellular matrix metabolism in chondrocytes to anabolism.
      (© 2024. The Author(s).)
    • Comments:
      Erratum in: Mol Biol Rep. 2024 Nov 16;51(1):1158. doi: 10.1007/s11033-024-10081-y. (PMID: 39549169)
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    • Contributed Indexing:
      Keywords: Articular cartilage; Disuse atrophy; Mechanical loading; Reversibility; Subchondral bone
    • Accession Number:
      EC 3.4.24.- (ADAMTS5 Protein)
      EC 3.4.24.- (Matrix Metalloproteinase 13)
      0 (Col2a1 protein, mouse)
      EC 3.4.24.- (Adamts5 protein, mouse)
      0 (SOX9 Transcription Factor)
      0 (Aggrecans)
      0 (Collagen Type II)
      0 (Sox9 protein, mouse)
      0 (Acan protein, mouse)
      EC 3.4.24.- (Mmp13 protein, mouse)
    • Publication Date:
      Date Created: 20240927 Date Completed: 20240927 Latest Revision: 20241118
    • Publication Date:
      20250114
    • Accession Number:
      PMC11436453
    • Accession Number:
      10.1007/s11033-024-09955-y
    • Accession Number:
      39331223