Human osteoclasts in vitro are both inhibited and stimulated dose dependently by cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)

Simone S. R. Nielsen, Juliana A. Z. Pedersen, Neha Sharma, Pernille K. Wasehuus, Anaïs Marie Julie Møller, Teis Esben Søndergaard, Kent Søe*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

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Abstrakt

Background
Conditions such as chronic pain have shown great benefit from cannabis treatment. However, there is a lack of well-controlled clinical trials to provide clarity on side-effects of cannabidiol therapeutics. We studied the effect of CBD and THC on osteoclasts and osteoblasts in vitro.
Methods
CD14+ monocytes from anonymous blood donors were differentiated into osteoclasts in vitro over 9 days using 25 ng/ml of both, M-CSF and RANKL. CBD and THC were purified from cannabis extracts by HPLC-DAD-HRMS. Osteoblasts were cultured from outgrowths of human bone. CBD or THC were added during osteoclast differentiation (7 days) and in mono- or co-cultures on bone slices (3 days) (0.3 to 100 µM; ≥5 technical replicates/condition).
Results
CBD and THC stimulated bone resorption at doses ranging from 1 to 10 µM (n=6 experiments) (eroded surface/BS: CBD, p=0.003; THC, p=0.012). However, doses of 30 µM CBD and THC inhibited osteoclastic bone resorption (Eroded surface/BS : CBD, p=0.03; THC, p=0.03 ) (Fig1 and 2). CBD and THC inhibited fusion at >10 µM (n=5) (osteoclasts/field: CBD, p=0.03; THC, p=0.03) (nuclei/osteoclast: - CBD, p=0.03; THC, p= 0.03). Western blotting confirmed expression of endocannabinoid receptor, CB1 in osteoclasts. CBD and THC, in co-culture settings (n=3 experiments) displayed dose dependent inhibition of osteoclastic bone resorption (representative values from 1 experiment CBD, p<0.0001; THC, p=0.0012) and ALP activity of osteoblasts (CBD, p<0.0001; THC, p=0.0005). These experiments suggest that osteoblasts are more sensitive to CBD and THC than osteoclasts.
Conclusion
Osteoclastic differentiation and bone resorption are directly affected by CBD and THC possibly through CB1. Considering all experiments, our study suggests that overall, both drugs enhance resorption at low doses and suppresses it at higher doses. Generally, our data suggest that both drugs may trigger bone loss and accelerate osteoporosis in vivo.
OriginalsprogEngelsk
Artikelnummer101400
TidsskriftBone Reports
Vol/bind16
Udgave nummerSuppl.
Sider (fra-til)40-41
ISSN2352-1872
DOI
StatusUdgivet - maj 2022
BegivenhedEuropean Calcified Tissue Society Congress - Helsinki, Finland
Varighed: 7. maj 202210. maj 2022

Konference

KonferenceEuropean Calcified Tissue Society Congress
Land/OmrådeFinland
ByHelsinki
Periode07/05/202210/05/2022

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