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Updated: Apr 13, 2026

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice
A Sophocleous1, A E Börjesson1, D M Salter2
1Rheumatology and Bone Diseases Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Objective:
Cannabinoid receptors and their ligands have been implicated in the regulation of various physiological processes but their role in osteoarthritis has not been investigated. The aim of this study was to evaluate the role of the type 2 cannabinoid receptor (Cnr2) in regulating susceptibility to osteoarthritis in mice.
Methods:
We analysed the severity of knee osteoarthritis as assessed by the Osteoarthritis Research Society International (OARSI) scoring system in mice with targeted deletion of Cnr2 (Cnr2(-/-)) and wild type (WT) littermates. Studies were conducted in mice subjected to surgical destabilisation of the medial meniscus (DMM) and in those with spontaneous age-related osteoarthritis (OA).
Results:
Osteoarthritis was more severe following DMM in the medial compartment of the knee in Cnr2(-/-) compared with WT mice (mean ± sem score = 4.9 ± 0.5 vs 3.6 ± 0.3; P = 0.017). Treatment of WT mice with the CB2-selective agonist HU308 following DMM reduced the severity of OA in the whole joint (HU308 = 8.4 ± 0.2 vs vehicle = 10.4 ± 0.6; P = 0.007). Spontaneous age related osteoarthritis was also more severe in the medial compartment of the knee in 12-month old Cnr2(-/-) mice compared with WT (5.6 ± 0.5 vs 3.5 ± 0.3, P = 0.008). Cultured articular chondrocytes from Cnr2(-/-) mice produced less proteoglycans in vitro than wild type chondrocytes.
Conclusion:
These studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect. Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted.
Insights
The type 2 cannabinoid receptor (Cnr2) pathway plays a key role in osteoarthritis development. Activating CB2 receptors showed a protective effect, suggesting a therapeutic target for osteoarthritis.
Area of Science:
- Biomedical Science
- Molecular Biology
- Immunology
Background:
- Cannabinoid receptors regulate physiological processes.
- The role of cannabinoid receptors in osteoarthritis (OA) remains largely unexplored.
- Type 2 cannabinoid receptor (Cnr2) is a potential target for OA research.
Purpose of the Study:
- To investigate the role of Cnr2 in OA susceptibility in mice.
- To evaluate the impact of Cnr2 deletion on OA development.
- To assess the therapeutic potential of CB2 receptor activation in OA.
Main Methods:
- Osteoarthritis severity was assessed using the OARSI scoring system in Cnr2 knockout (Cnr2(-/-)) and wild-type (WT) mice.
- OA was induced by surgical destabilization of the medial meniscus (DMM) or occurred spontaneously with age.
- Pharmacological activation of CB2 receptors was tested using the selective agonist HU308.
Main Results:
- Cnr2(-/-) mice exhibited more severe knee osteoarthritis after DMM compared to WT mice.
- Pharmacological activation of CB2 receptors with HU308 reduced OA severity in WT mice.
- Age-related spontaneous OA was also more severe in Cnr2(-/-) mice, with reduced proteoglycan production by chondrocytes.
Conclusions:
- The Cnr2 pathway is implicated in the pathophysiology of osteoarthritis in mice.
- Pharmacological activation of CB2 receptors demonstrates a protective effect against OA.
- Further research into cannabinoid receptors in human OA pathogenesis is warranted.
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