Accelerated post traumatic osteoarthritis in a dual injury murine model

Kendal McCulloch, Carmen Huesa, Lynette Dunning, Gary J. Litherland, Rob J. Van't Hof, John C. Lockhart, Carl S. Goodyear

Research output: Contribution to journalArticle

Abstract

Objective
Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g. sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised
medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates OA pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.

Methods
OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.

Results
Osteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and CS. Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.

Conclusion
Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple
pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.
Original languageEnglish
JournalOsteoarthritis and Cartilage
Early online date5 Jul 2019
DOIs
Publication statusE-pub ahead of print - 5 Jul 2019

Fingerprint

Cartilage
Osteoarthritis
Wounds and Injuries
Ligaments
Osteophyte
Bearings (structural)
Synovitis
Joints
Surgery
Weight-Bearing
Articular Cartilage
Pathology
Pain
Osteitis
X-Ray Microtomography
Athletic Injuries
Ambulatory Surgical Procedures
Inbred C57BL Mouse
Histology
Sports

Keywords

  • Post-traumatic osteoarthritis
  • Osteophytes
  • Synovitis
  • Pain
  • Osteoarthritis models

Cite this

@article{1cfe10c81c784d3f84d17270dbf8ea24,
title = "Accelerated post traumatic osteoarthritis in a dual injury murine model",
abstract = "ObjectiveJoint injury involving destabilisation of the joint and damage to the articular cartilage (e.g. sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilisedmedial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates OA pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.MethodsOA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.ResultsOsteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and CS. Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.ConclusionJoint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiplepathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.",
keywords = "Post-traumatic osteoarthritis, Osteophytes, Synovitis, Pain, Osteoarthritis models",
author = "Kendal McCulloch and Carmen Huesa and Lynette Dunning and Litherland, {Gary J.} and {Van't Hof}, {Rob J.} and Lockhart, {John C.} and Goodyear, {Carl S.}",
year = "2019",
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language = "English",
journal = "Osteoarthritis and Cartilage",
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Accelerated post traumatic osteoarthritis in a dual injury murine model. / McCulloch, Kendal; Huesa, Carmen; Dunning, Lynette; Litherland, Gary J.; Van't Hof, Rob J.; Lockhart, John C.; Goodyear, Carl S.

In: Osteoarthritis and Cartilage, 05.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accelerated post traumatic osteoarthritis in a dual injury murine model

AU - McCulloch, Kendal

AU - Huesa, Carmen

AU - Dunning, Lynette

AU - Litherland, Gary J.

AU - Van't Hof, Rob J.

AU - Lockhart, John C.

AU - Goodyear, Carl S.

PY - 2019/7/5

Y1 - 2019/7/5

N2 - ObjectiveJoint injury involving destabilisation of the joint and damage to the articular cartilage (e.g. sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilisedmedial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates OA pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.MethodsOA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.ResultsOsteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and CS. Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.ConclusionJoint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiplepathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.

AB - ObjectiveJoint injury involving destabilisation of the joint and damage to the articular cartilage (e.g. sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilisedmedial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates OA pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.MethodsOA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.ResultsOsteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and CS. Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.ConclusionJoint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiplepathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.

KW - Post-traumatic osteoarthritis

KW - Osteophytes

KW - Synovitis

KW - Pain

KW - Osteoarthritis models

U2 - 10.1016/j.joca.2019.05.027

DO - 10.1016/j.joca.2019.05.027

M3 - Article

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

SN - 1063-4584

ER -