The catabolic-to-anabolic shift seen in the canine osteoarthritic cartilage treated with knee joint distraction occurs after the distraction period

M. Teunissen, B.P. Meij, L. Snel, K. Coeleveld, J. Popov-Celeketic, I.S. Ludwig, F. Broere, F.P.J.G. Lafeber, M.A. Tryfonidou, S.C. Mastbergen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background
Cartilage regenerative mechanisms initiated by knee joint distraction (KJD) remain elusive. Animal experiments that are representative for the human osteoarthritic situation and investigate the effects of KJD at consecutive time points could be helpful in this respect but are lacking. This study investigated the effects of KJD on the osteoarthritic joint of dogs on two consecutive timepoints.

Methods
Osteoarthritis was bilaterally induced for 10 weeks in 12 dogs using the groove model. Subsequently, KJD was applied to the right hindlimb for 8 weeks. The cartilage, subchondral bone and synovial membrane were investigated directly after KJD treatment, and after 10 weeks of follow-up after KJD treatment. Macroscopic and microscopic joint tissue alterations were investigated using the OARSI grading system. Additionally, proteoglycan content and synthesis of the cartilage were assessed biochemically. RT-qPCR analysis was used to explore involved signaling pathways.

Results
Directly after KJD proteoglycan and collagen type II content were reduced accompanied by decreased proteoglycan synthesis. After 10 weeks of follow-up, proteoglycan and collagen type II content were partly restored and proteoglycan synthesis increased. RT-qPCR analysis of the cartilage suggests involvement of the TGF-β and Notch signalling pathways. Additionally, increased subchondral bone remodelling was found at 10 weeks of follow-up.

Conclusion
While the catabolic environment in the cartilage is still present directly after KJD, at 10 weeks of follow-up a switch towards a more anabolic joint environment was observed. Further investigation of this timepoint and the pathways involved might elucidate the regenerative mechanisms behind KJD.

The Translational Potential of this Article
Further elucidation of the regenerative mechanisms behind KJD could improve the existing KJD treatment. Furthermore, these findings could provide input for the discovery or improvement of other joint regenerative treatment strategies.
Original languageEnglish
Pages (from-to)44-55
Number of pages12
JournalJournal of Orthopaedic Translation
Volume38
Early online date20 Oct 2022
DOIs
Publication statusPublished - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Funding

This project was financially supported by the Dutch Arthritis Society ( LLP9 and LLP22 ) and NWO Domain Applied and Engineering Sciences (AES) ( P15-23 ). There is no further involvement in the present work of the abovementioned sources.

FundersFunder number
LLP9LLP22
NWO Domain Applied and Engineering Sciences
AES CorporationP15-23
Dutch Arthritis Society

    Keywords

    • Canine
    • Knee joint distraction
    • Mechanical loading
    • Proteoglycans
    • TGF-β signalling

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