Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

Michelle Teunissen; Alberto Miranda Bedate; Katja Coeleveld; Frank M Riemers; Björn P Meij; Floris P J G Lafeber; Marianna A Tryfonidou; Simon C Mastbergen

doi:10.1177/19476035211014595

Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

Michelle Teunissen
, Alberto Miranda Bedate
, Katja Coeleveld
, Frank M Riemers
, Björn P Meij
, Floris P J G Lafeber
, Marianna A Tryfonidou
, Simon C Mastbergen

CS_Locomotion

University Medical Center Utrecht
Utrecht University, University Medical Center Utrecht

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process.

DESIGN: Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining.

RESULTS: Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example, ADAMTS5, MMP9, MMP13, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased.

CONCLUSIONS: Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

Original language	English
Pages (from-to)	1654S-1664S
Journal	Cartilage
Volume	13
Issue number	2_suppl
Early online date	20 May 2021
DOIs	https://doi.org/10.1177/19476035211014595
Publication status	Published - 1 Dec 2021

Bibliographical note

Funding Information:
The authors would like to thank P. M. Roermund for his assistance during application of the distraction device in the in vivo experiment. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was financially supported by the Dutch Arthritis Society (LLP9 and LLP22) and NWO Applied and Engineering Sciences (P15-23). There is no further involvement in the present work of the above-mentioned sources.

Publisher Copyright:
© The Author(s) 2021.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cartilage regeneration
groove model
osteoarthritis

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19476035211014595Final published version, 591 KBLicence: CC BY

Cite this

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title = "Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction",

abstract = "OBJECTIVE: Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process.DESIGN: Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining.RESULTS: Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example, ADAMTS5, MMP9, MMP13, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased.CONCLUSIONS: Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.",

keywords = "cartilage regeneration, groove model, osteoarthritis",

author = "Michelle Teunissen and \{Miranda Bedate\}, Alberto and Katja Coeleveld and Riemers, \{Frank M\} and Meij, \{Bj{\"o}rn P\} and Lafeber, \{Floris P J G\} and Tryfonidou, \{Marianna A\} and Mastbergen, \{Simon C\}",

note = "Funding Information: The authors would like to thank P. M. Roermund for his assistance during application of the distraction device in the in vivo experiment. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was financially supported by the Dutch Arthritis Society (LLP9 and LLP22) and NWO Applied and Engineering Sciences (P15-23). There is no further involvement in the present work of the above-mentioned sources. Publisher Copyright: {\textcopyright} The Author(s) 2021.",

year = "2021",

month = dec,

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doi = "10.1177/19476035211014595",

language = "English",

volume = "13",

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T1 - Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

AU - Teunissen, Michelle

AU - Miranda Bedate, Alberto

AU - Coeleveld, Katja

AU - Riemers, Frank M

AU - Meij, Björn P

AU - Lafeber, Floris P J G

AU - Tryfonidou, Marianna A

AU - Mastbergen, Simon C

N1 - Funding Information: The authors would like to thank P. M. Roermund for his assistance during application of the distraction device in the in vivo experiment. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was financially supported by the Dutch Arthritis Society (LLP9 and LLP22) and NWO Applied and Engineering Sciences (P15-23). There is no further involvement in the present work of the above-mentioned sources. Publisher Copyright: © The Author(s) 2021.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - OBJECTIVE: Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process.DESIGN: Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining.RESULTS: Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example, ADAMTS5, MMP9, MMP13, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased.CONCLUSIONS: Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

AB - OBJECTIVE: Joint distraction triggers intrinsic cartilage repair in animal models of osteoarthritis (OA), corroborating observations in human OA patients treated with joint distraction. The present study explores the still largely elusive mechanism initiating this repair process.DESIGN: Unilateral OA was induced in the knee joint of 8 dogs using the groove model; the contralateral joint served as a control. After 10 weeks, 4 animals received joint distraction, the other 4 serving as OA controls. Halfway the distraction period (after 4 weeks of a standard 8-week distraction treatment), all animals were euthanized, and joint tissues were collected. A targeted quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed of commonly involved processes including matrix catabolism/anabolism, inflammation, and known signaling pathways in OA. In addition, cartilage changes were determined on tissue sections using the canine OARSI (Osteoarthritis Research Society International) histopathology score and collagen type II (COL2A1) immunostaining.RESULTS: Midway distraction, the distracted OA joint showed an upregulation of proteolytic genes, for example, ADAMTS5, MMP9, MMP13, compared to OA alone and the healthy joints, which correlated with an increased OARSI score. Additionally, genes of the transforming growth factor (TGF)-β and Notch pathway, and markers associated with progenitor cells were increased.CONCLUSIONS: Joint distraction initiates both catabolic and anabolic transcriptional responses. The enhanced turnover, and thereby renewal of the matrix, could be the key to the cartilage repair observed in the months after joint distraction.

KW - cartilage regeneration

KW - groove model

KW - osteoarthritis

UR - https://www.scopus.com/pages/publications/85106433729

U2 - 10.1177/19476035211014595

DO - 10.1177/19476035211014595

M3 - Article

C2 - 34014119

SN - 1947-6035

VL - 13

SP - 1654S-1664S

JO - Cartilage

JF - Cartilage

IS - 2_suppl

ER -

Enhanced Extracellular Matrix Breakdown Characterizes the Early Distraction Phase of Canine Knee Joint Distraction

Abstract

Bibliographical note

UN SDGs

Keywords

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