Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis

L. Longobardi, J. D. Temple, L. Tagliafierro, H. Willcockson, A. Esposito, N. D'Onofrio, E. Stein, T. Li, T. J. Myers, H. Ozkan, M. L. Balestrieri, V. Ulici, R. F. Loeser, A. Spagnoli

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objective We previously found in our embryonic studies that proper regulation of the chemokine CCL12 through its sole receptor CCR2, is critical for joint and growth plate development. In the present study, we examined the role of CCR2 in injury-induced-osteoarthritis (OA). Method We used a murine model of injury-induced-OA (destabilization of medial meniscus, DMM), and systemically blocked CCR2 using a specific antagonist (RS504393) at different times during disease progression. We examined joint degeneration by assessing cartilage (cartilage loss, chondrocyte hypertrophy, MMP-13 expression) and bone lesions (bone sclerosis, osteophytes formation) with or without the CCR2 antagonist. We also performed pain behavioral studies by assessing the weight distribution between the normal and arthritic hind paws using the IITS incapacitance meter. Results Testing early vs delayed administration of the CCR2 antagonist demonstrated differential effects on joint damage. We found that OA changes in articular cartilage and bone were ameliorated by pharmacological CCR2 blockade, if given early in OA development: specifically, pharmacological targeting of CCR2 during the first 4 weeks (wks) following injury, reduced OA cartilage and bone damage, with less effectiveness with later treatments. Importantly, our pain-related behavioral studies showed that blockade of CCR2 signaling during early, 1–4 wks post-surgery or moderate, 4–8 wks post-surgery, OA was sufficient to decrease pain measures, with sustained improvement at later stages, after treatment was stopped. Conclusions Our data highlight the potential efficacy of antagonizing CCR2 at early stages to slow the progression of post-injury OA and, in addition, improve pain symptoms.

Original languageEnglish (US)
Pages (from-to)914-925
Number of pages12
JournalOsteoarthritis and Cartilage
Volume25
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • Animal model
  • Bone
  • Cartilage
  • Chemokines
  • Joint disease
  • Osteoarthritis

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

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    Longobardi, L., Temple, J. D., Tagliafierro, L., Willcockson, H., Esposito, A., D'Onofrio, N., Stein, E., Li, T., Myers, T. J., Ozkan, H., Balestrieri, M. L., Ulici, V., Loeser, R. F., & Spagnoli, A. (2017). Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis. Osteoarthritis and Cartilage, 25(6), 914-925. https://doi.org/10.1016/j.joca.2016.11.004