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Updated: Mar 14, 2026
Destabilization of the Medial Meniscus and Cartilage Scratch Murine Model of Accelerated Osteoarthritis
Published on: July 6, 2022
Spinal microglial activation in a murine surgical model of knee osteoarthritis
P B Tran1, R E Miller2, S Ishihara1
1Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W. Harrison St, Suite 510, Chicago, IL, USA.
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.
Insights
Destabilization of the medial meniscus (DMM) causes late-onset microgliosis and pain in mice. This microgliosis, linked to joint damage, is reduced in Adamts5 null mice, suggesting a role in chronic pain.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Microgliosis, the activation of microglia, is implicated in chronic pain development.
- Neuronal fractalkine (CX3CL1) signaling is a known contributor to microgliosis.
Purpose of the Study:
- To investigate the temporal profile of dorsal horn microgliosis following destabilization of the medial meniscus (DMM) in wild-type (WT) and Adamts5 null mice.
- To assess the release of fractalkine (FKN) from dorsal root ganglia (DRG) cultures after DMM.
Main Methods:
- DMM or sham surgery in WT, CX3CR1-GFP, and Adamts5 null mice.
- Monitoring hind paw mechanical allodynia using von Frey fibers.
- Assessing dorsal horn microgliosis via Iba1 staining and DRG cell cultures for FKN ELISA.
Main Results:
- WT mice showed increased microgliosis at 8 and 16 weeks post-DMM, correlating with increased FKN release.
- Adamts5 null mice were protected from mechanical allodynia and did not exhibit increased FKN release or dorsal horn microgliosis.
- Sham surgery did not induce microgliosis.
Conclusions:
- DMM surgery induces late-stage dorsal horn microgliosis, potentially mediated by DRG FKN release.
- The absence of microgliosis and pain in Adamts5 null mice suggests microgliosis is linked to joint damage and persistent pain.
