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Osteoarthritis Cartilage. 2017 May;25(5):718-726. doi: 10.1016/j.joca.2016.09.007. Epub 2016 Sep 16.

Spinal microglial activation in a murine surgical model of knee osteoarthritis.

Author information

1
Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA.
2
Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA; Department of Biochemistry, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA.
3
Department of Pharmacology, Northwestern University, Chicago, IL, USA.
4
Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA; Department of Biochemistry, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA. Electronic address: anne-marie_malfait@rush.edu.

Abstract

OBJECTIVE:

Microgliosis, the activation of microglial cells, is thought to contribute to synaptic transmission in the dorsal horn and thereby promote chronic pain. The primary aim of this study was to document the temporal profile of dorsal horn microgliosis after destabilization of the medial meniscus (DMM) in wild type (WT) and Adamts5 null mice. Since neuronal fractalkine (CX3CL1) contributes to microgliosis, we assessed its release from dorsal root ganglia (DRG) cultures after DMM.

DESIGN:

DMM or sham surgery was performed in the right knee of 10-week old male WT, CX3CR1-green fluorescent protein (GFP), or Adamts5 null C57BL/6 mice. Hind paw mechanical allodynia was monitored using von Frey fibers. L4 dorsal horn microgliosis was assessed 4, 8 and 16 weeks after surgery, based on the morphology of Iba1-immunoreactive microglia. DRG cells (L3-L5) were cultured and supernatants collected for fractalkine (FKN) ELISA.

RESULTS:

In WT mice, numbers of activated microglia were increased 8 and 16 weeks, but not 4 weeks, after DMM but not sham surgery. DRG cultures showed increased basal FKN release at 8 and 16 weeks. Adamts5 null mice did not develop mechanical allodynia up to 16 weeks after DMM. Accordingly, DRG cultures from these mice did not exhibit increased FKN release and dorsal horn microgliosis did not occur.

CONCLUSION:

DMM surgery leads to late stage dorsal horn microgliosis. The temporal correlation with DRG FKN release suggests it may contribute to microgliosis. Reduced microgliosis in Adamts5 null mice, which are protected from joint damage and associated mechanical allodynia after DMM, suggests that microgliosis is associated with joint damage and accompanying persistent pain.

KEYWORDS:

Allodynia; Fractalkine; Microglia; Mouse; Osteoarthritis; Pain

PMID:
27646532
PMCID:
PMC5354992
DOI:
10.1016/j.joca.2016.09.007
[Indexed for MEDLINE]
Free PMC Article

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