PAR2 accelerates osteoarthritis-like joint changes in a murine model of post-traumatic osteoarthritis

Carl Goodyear, K. McCulloch, C. Huesa, L. Dunning, R. van 't Hof, J. Lockhart

Research output: Contribution to journalMeeting Abstract

Abstract

Background Post-traumatic osteoarthritis (PTOA) is associated with articular cartilage damage and represents a major clinical challenge due to the poor regenerative capability of cartilage. We have recently developed a novel and robust dual injury murine model of PTOA, which combines destabilisation of the medial meniscus (DMM) and cartilage scratch1. This model results in accelerated OA-like symptoms including enhanced osteophyogenesis. Prior studies in the DMM model have demonstrated that absence of proteinase-activated receptor 2 (PAR2) in mice results in significant protection from early OA-like symptoms. 
Objectives To investigate if the absence of PAR2 confers protection in a dual injury PTOA murine model.
Methods PTOA was induced in both male C57BL/6 wild-type (WT) and PAR2-/- mice, via combined destabilisation of the medial meniscus and cartilage scratch (DCS). Twenty-eight days post-surgery, osteophytogenesis and bone changes were monitored using microcomputered tomography. Dynamic weight bearing was assessed as an indirect measurement of pain at day 14.
Results Evaluation of the presence and number of osteophyte revealed no significant differences between WT and PAR2-/- mice at day 28. However, quantification of osteophytes revealed that PAR2-/- mice had significantly smaller osteophytes (p=0.006) with less mineralised bone (p=0.003). Moreover, analysis of metaphyseal trabecular bone on the operated leg showed a significant decrease in % bone volume/tissue volume (BV/TV) (p=0.025). Assessment of pain-related behaviour, using dynamic weight bearing at day 14, demonstrated that PAR2-/- mice exerted less load on their front paws.
Conclusion The findings in this study show that PAR2 plays a role in accelerated OA-like symptoms (i.e., osteophyte formation) in a dual injury model of OA, where both destabilisation of the medial meniscus and cartilage damage drive disease pathology. Furthermore, the loss of PAR2 decreases pain behaviour suggesting that PAR2 is involved in pain sensing. Taken together, these results support the future exploration of PAR2 as a therapeutic target for PTOA.
Original languageEnglish
Pages (from-to)110-110
Number of pages1
JournalAnnals of the Rheumatic Diseases
Volume78
Issue numberIssue Suppl 2
Early online date27 May 2019
DOIs
Publication statusPublished - 27 Jun 2019
EventEULAR 2019: European College of Rheumatology - Feria de Madrid, Madrid, Spain
Duration: 12 Jun 201915 Jun 2019
https://www.congress.eular.org/?utm_source=google&utm_medium=ads&utm_campaign=registration&gclid=EAIaIQobChMIwZKF_-Wh4AIVB53VCh1iIgucEAAYASAAEgJkFfD_BwE

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PAR-2 Receptor
Osteoarthritis
Joints
Cartilage
Tibial Meniscus
Osteophyte
Bone
Bearings (structural)
Weight-Bearing
Pain Measurement
Bone and Bones
Wounds and Injuries
Pain
Articular Cartilage
Pathology
Ambulatory Surgical Procedures
Surgery
Tomography
Leg

Keywords

  • PAR2
  • Osteoarthritis
  • Osteophytes

Cite this

@article{e05e2d1371fb44bdbf2557ad564a1802,
title = "PAR2 accelerates osteoarthritis-like joint changes in a murine model of post-traumatic osteoarthritis",
abstract = "Background Post-traumatic osteoarthritis (PTOA) is associated with articular cartilage damage and represents a major clinical challenge due to the poor regenerative capability of cartilage. We have recently developed a novel and robust dual injury murine model of PTOA, which combines destabilisation of the medial meniscus (DMM) and cartilage scratch1. This model results in accelerated OA-like symptoms including enhanced osteophyogenesis. Prior studies in the DMM model have demonstrated that absence of proteinase-activated receptor 2 (PAR2) in mice results in significant protection from early OA-like symptoms. Objectives To investigate if the absence of PAR2 confers protection in a dual injury PTOA murine model.Methods PTOA was induced in both male C57BL/6 wild-type (WT) and PAR2-/- mice, via combined destabilisation of the medial meniscus and cartilage scratch (DCS). Twenty-eight days post-surgery, osteophytogenesis and bone changes were monitored using microcomputered tomography. Dynamic weight bearing was assessed as an indirect measurement of pain at day 14.Results Evaluation of the presence and number of osteophyte revealed no significant differences between WT and PAR2-/- mice at day 28. However, quantification of osteophytes revealed that PAR2-/- mice had significantly smaller osteophytes (p=0.006) with less mineralised bone (p=0.003). Moreover, analysis of metaphyseal trabecular bone on the operated leg showed a significant decrease in {\%} bone volume/tissue volume (BV/TV) (p=0.025). Assessment of pain-related behaviour, using dynamic weight bearing at day 14, demonstrated that PAR2-/- mice exerted less load on their front paws.Conclusion The findings in this study show that PAR2 plays a role in accelerated OA-like symptoms (i.e., osteophyte formation) in a dual injury model of OA, where both destabilisation of the medial meniscus and cartilage damage drive disease pathology. Furthermore, the loss of PAR2 decreases pain behaviour suggesting that PAR2 is involved in pain sensing. Taken together, these results support the future exploration of PAR2 as a therapeutic target for PTOA.",
keywords = "PAR2, Osteoarthritis, Osteophytes",
author = "Carl Goodyear and K. McCulloch and C. Huesa and L. Dunning and {van 't Hof}, R. and J. Lockhart",
year = "2019",
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doi = "10.1136/annrheumdis-2019-eular.6311",
language = "English",
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}

PAR2 accelerates osteoarthritis-like joint changes in a murine model of post-traumatic osteoarthritis. / Goodyear, Carl; McCulloch, K.; Huesa, C.; Dunning, L.; van 't Hof, R.; Lockhart, J.

In: Annals of the Rheumatic Diseases, Vol. 78, No. Issue Suppl 2, 27.06.2019, p. 110-110.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - PAR2 accelerates osteoarthritis-like joint changes in a murine model of post-traumatic osteoarthritis

AU - Goodyear, Carl

AU - McCulloch, K.

AU - Huesa, C.

AU - Dunning, L.

AU - van 't Hof, R.

AU - Lockhart, J.

PY - 2019/6/27

Y1 - 2019/6/27

N2 - Background Post-traumatic osteoarthritis (PTOA) is associated with articular cartilage damage and represents a major clinical challenge due to the poor regenerative capability of cartilage. We have recently developed a novel and robust dual injury murine model of PTOA, which combines destabilisation of the medial meniscus (DMM) and cartilage scratch1. This model results in accelerated OA-like symptoms including enhanced osteophyogenesis. Prior studies in the DMM model have demonstrated that absence of proteinase-activated receptor 2 (PAR2) in mice results in significant protection from early OA-like symptoms. Objectives To investigate if the absence of PAR2 confers protection in a dual injury PTOA murine model.Methods PTOA was induced in both male C57BL/6 wild-type (WT) and PAR2-/- mice, via combined destabilisation of the medial meniscus and cartilage scratch (DCS). Twenty-eight days post-surgery, osteophytogenesis and bone changes were monitored using microcomputered tomography. Dynamic weight bearing was assessed as an indirect measurement of pain at day 14.Results Evaluation of the presence and number of osteophyte revealed no significant differences between WT and PAR2-/- mice at day 28. However, quantification of osteophytes revealed that PAR2-/- mice had significantly smaller osteophytes (p=0.006) with less mineralised bone (p=0.003). Moreover, analysis of metaphyseal trabecular bone on the operated leg showed a significant decrease in % bone volume/tissue volume (BV/TV) (p=0.025). Assessment of pain-related behaviour, using dynamic weight bearing at day 14, demonstrated that PAR2-/- mice exerted less load on their front paws.Conclusion The findings in this study show that PAR2 plays a role in accelerated OA-like symptoms (i.e., osteophyte formation) in a dual injury model of OA, where both destabilisation of the medial meniscus and cartilage damage drive disease pathology. Furthermore, the loss of PAR2 decreases pain behaviour suggesting that PAR2 is involved in pain sensing. Taken together, these results support the future exploration of PAR2 as a therapeutic target for PTOA.

AB - Background Post-traumatic osteoarthritis (PTOA) is associated with articular cartilage damage and represents a major clinical challenge due to the poor regenerative capability of cartilage. We have recently developed a novel and robust dual injury murine model of PTOA, which combines destabilisation of the medial meniscus (DMM) and cartilage scratch1. This model results in accelerated OA-like symptoms including enhanced osteophyogenesis. Prior studies in the DMM model have demonstrated that absence of proteinase-activated receptor 2 (PAR2) in mice results in significant protection from early OA-like symptoms. Objectives To investigate if the absence of PAR2 confers protection in a dual injury PTOA murine model.Methods PTOA was induced in both male C57BL/6 wild-type (WT) and PAR2-/- mice, via combined destabilisation of the medial meniscus and cartilage scratch (DCS). Twenty-eight days post-surgery, osteophytogenesis and bone changes were monitored using microcomputered tomography. Dynamic weight bearing was assessed as an indirect measurement of pain at day 14.Results Evaluation of the presence and number of osteophyte revealed no significant differences between WT and PAR2-/- mice at day 28. However, quantification of osteophytes revealed that PAR2-/- mice had significantly smaller osteophytes (p=0.006) with less mineralised bone (p=0.003). Moreover, analysis of metaphyseal trabecular bone on the operated leg showed a significant decrease in % bone volume/tissue volume (BV/TV) (p=0.025). Assessment of pain-related behaviour, using dynamic weight bearing at day 14, demonstrated that PAR2-/- mice exerted less load on their front paws.Conclusion The findings in this study show that PAR2 plays a role in accelerated OA-like symptoms (i.e., osteophyte formation) in a dual injury model of OA, where both destabilisation of the medial meniscus and cartilage damage drive disease pathology. Furthermore, the loss of PAR2 decreases pain behaviour suggesting that PAR2 is involved in pain sensing. Taken together, these results support the future exploration of PAR2 as a therapeutic target for PTOA.

KW - PAR2

KW - Osteoarthritis

KW - Osteophytes

UR - https://www.congress.eular.org/

U2 - 10.1136/annrheumdis-2019-eular.6311

DO - 10.1136/annrheumdis-2019-eular.6311

M3 - Meeting Abstract

VL - 78

SP - 110

EP - 110

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - Issue Suppl 2

ER -