The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice
Open accessAbstract
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.
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The CB2 receptor agonist HU308 reduced joint damage in the DMM osteoarthritis model.
“The CB 2 receptor agonist HU308 reduced joint damage in the DMM osteoarthritis model, whereas CB 2 ( -/ -) mice developed more joint damage than wildtype mice (Sophocleous et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sophocleous et al, 2015
CB2-/- mice developed more joint damage than wildtype mice in the DMM osteoarthritis model.
“whereas CB 2 ( -/ -) mice developed more joint damage than wildtype mice (Sophocleous et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sophocleous et al, 2015
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- Authors
- Sophocleous, A., Börjesson, A. E., Salter, D. M., & Ralston, S. H.
- Affiliations
- Western General Hospital (GB)
- Institute of Genetics and Cancer (GB)
- Corresponding author
- Sophocleous, A.
- Börjesson, A.E.
- Salter, D.M.
- Ralston, S.H.
- Venue
- Osteoarthritis and Cartilage
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 23
- Issue
- 9
- Pages
- 1586-1594
- ISSN
- 1063-4584 (ISSN-L)
- OpenAlex
- W2066638828
- Cited by
- 54
- References
- 34
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 2 · 2016: 3
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Osteoarthritis and Cartilage (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Funders
- Versus Arthritis (17713)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone and Joint Diseases
- Keywords
- CB2 receptor, osteoarthritis, knee osteoarthritis, age-related osteoarthritis, HU-308, CB2 receptor agonist, articular chondrocytes, proteoglycan synthesis, chondrocyte hypertrophy, cannabinoid receptors
- MeSH terms
- Aging, Animals, Cannabinoids, Disease Susceptibility, Menisci, Tibial, Osteoarthritis, Proteoglycans, Chondrocytes, Osteoarthritis, Knee, Receptor, Cannabinoid, CB2, Mice, X-Ray Microtomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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