Abstract
Legalized use of cannabis for medical or recreational use is becoming more and more common. With respect to
potential side-effects on bone health only few clinical trials have been conducted – and with opposing results.
Therefore, it seems that there is a need for more knowledge on the potential effects of cannabinoids on human
bone cells. We studied the effect of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) (dose range from 0.3
to 30 μM) on human osteoclasts in mono- as well as in co-cultures with human osteoblast lineage cells. We have
used CD14+ monocytes from anonymous blood donors to differentiate into osteoclasts, and human osteoblast
lineage cells from outgrowths of human trabecular bone. Our results show that THC and CBD have dosedependent
effects on both human osteoclast fusion and bone resorption. In the lower dose ranges of THC and
CBD, osteoclast fusion was unaffected while bone resorption was increased. At higher doses, both osteoclast
fusion and bone resorption were inhibited. In co-cultures, both osteoclastic bone resorption and alkaline phosphatase
activity of the osteoblast lineage cells were inhibited. Finally, we observed that the cannabinoid receptor
CNR2 is more highly expressed than CNR1 in CD14+ monocytes and pre-osteoclasts, but also that differentiation
to osteoclasts was coupled to a reduced expression of CNR2, in particular. Interestingly, under co-culture conditions,
we only detected the expression of CNR2 but not CNR1 for both osteoclast as well as osteoblast lineage
nuclei. In line with the existing literature on the effect of cannabinoids on bone cells, our current study shows
both stimulatory and inhibitory effects. This highlights that potential unfavorable effects of cannabinoids on
bone cells and bone health is a complex matter. The contradictory and lacking documentation for such potential
unfavorable effects on bone health as well as other potential effects, should
potential side-effects on bone health only few clinical trials have been conducted – and with opposing results.
Therefore, it seems that there is a need for more knowledge on the potential effects of cannabinoids on human
bone cells. We studied the effect of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) (dose range from 0.3
to 30 μM) on human osteoclasts in mono- as well as in co-cultures with human osteoblast lineage cells. We have
used CD14+ monocytes from anonymous blood donors to differentiate into osteoclasts, and human osteoblast
lineage cells from outgrowths of human trabecular bone. Our results show that THC and CBD have dosedependent
effects on both human osteoclast fusion and bone resorption. In the lower dose ranges of THC and
CBD, osteoclast fusion was unaffected while bone resorption was increased. At higher doses, both osteoclast
fusion and bone resorption were inhibited. In co-cultures, both osteoclastic bone resorption and alkaline phosphatase
activity of the osteoblast lineage cells were inhibited. Finally, we observed that the cannabinoid receptor
CNR2 is more highly expressed than CNR1 in CD14+ monocytes and pre-osteoclasts, but also that differentiation
to osteoclasts was coupled to a reduced expression of CNR2, in particular. Interestingly, under co-culture conditions,
we only detected the expression of CNR2 but not CNR1 for both osteoclast as well as osteoblast lineage
nuclei. In line with the existing literature on the effect of cannabinoids on bone cells, our current study shows
both stimulatory and inhibitory effects. This highlights that potential unfavorable effects of cannabinoids on
bone cells and bone health is a complex matter. The contradictory and lacking documentation for such potential
unfavorable effects on bone health as well as other potential effects, should
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 117035 |
| Tidsskrift | Bone |
| Vol/bind | 181 |
| ISSN | 8756-3282 |
| DOI | |
| Status | Udgivet - apr. 2024 |
Emneord
- Hash, Cannabis, Knogler
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