title: CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy.
abstract: The role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA.
  
  
  
  OA was induced in 10 weeks old male wild type (WT), Ccl2-/-and Ccr2-/-mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naïve and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance.
  
  
  
  Absence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average chondropathy score was observed in both Ccl2-/-and Ccr2-/-mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2-/-mice. Pain-related behaviour in Ccl2-/-and Ccr2-/-mice post DMM was delayed in onset.
  
  
  
  The CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage.
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Miotla Zarebska
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK.
authors.forename: A
authors.initials: A
authors.lastname: Chanalaris
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK.
authors.forename: C
authors.initials: C
authors.lastname: Driscoll
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK.
authors.forename: A
authors.initials: A
authors.lastname: Burleigh
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, Chicago, IL, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Miller
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, Chicago, IL, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Malfait
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK.
authors.forename: B
authors.initials: B
authors.lastname: Stott
authors.affiliation: Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, OX3 7FY, UK. Electronic address: Tonia.vincent@kennedy.ox.ac.uk.
authors.forename: T L
authors.initials: TL
authors.lastname: Vincent
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D054390:Receptors, CCR2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2
keywords: Animal model; CCL2; CCR2; Osteoarthritis; Pain