RGD Reference Report - CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis. - Rat Genome Database

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CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis.

Authors: Miller, RE  Tran, PB  Das, R  Ghoreishi-Haack, N  Ren, D  Miller, RJ  Malfait, AM 
Citation: Miller RE, etal., Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20602-7. doi: 10.1073/pnas.1209294110. Epub 2012 Nov 26.
RGD ID: 8661785
Pubmed: PMID:23185004   (View Abstract at PubMed)
PMCID: PMC3528555   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1209294110   (Journal Full-text)

Osteoarthritis is one of the leading causes of chronic pain, but almost nothing is known about the mechanisms and molecules that mediate osteoarthritis-associated joint pain. Consequently, treatment options remain inadequate and joint replacement is often inevitable. Here, we use a surgical mouse model that captures the long-term progression of knee osteoarthritis to longitudinally assess pain-related behaviors and concomitant changes in the innervating dorsal root ganglia (DRG). We demonstrate that monocyte chemoattractant protein (MCP)-1 (CCL2) and its high-affinity receptor, chemokine (C-C motif) receptor 2 (CCR2), are central to the development of pain associated with knee osteoarthritis. After destabilization of the medial meniscus, mice developed early-onset secondary mechanical allodynia that was maintained for 16 wk. MCP-1 and CCR2 mRNA, protein, and signaling activity were temporarily up-regulated in the innervating DRG at 8 wk after surgery. This result correlated with the presentation of movement-provoked pain behaviors, which were maintained up to 16 wk. Mice that lack Ccr2 also developed mechanical allodynia, but this started to resolve from 8 wk onwards. Despite severe allodynia and structural knee joint damage equal to wild-type mice, Ccr2-null mice did not develop movement-provoked pain behaviors at 8 wk. In wild-type mice, macrophages infiltrated the DRG by 8 wk and this was maintained through 16 wk after surgery. In contrast, macrophage infiltration was not observed in Ccr2-null mice. These observations suggest a key role for the MCP-1/CCR2 pathway in establishing osteoarthritis pain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Knee Osteoarthritis  ISOCcr2 (Mus musculus)8661785; 8661785mRNA and protein:increased expression:dorsal root ganglion:RGD 
Knee Osteoarthritis  IMP 8661785mRNA and protein:increased expression:dorsal root ganglion:RGD 
Pain  ISOCcr2 (Mus musculus)8661785; 8661785associated with Osteoarthritis and KneeRGD 
Pain  IEP 8661785associated with Osteoarthritis and KneeRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information