[The effects of glucocorticoid on expression of cannabinoid-1 receptors in osteoclasts from tibial proximal metaphysis of rats].
OBJECTIVE
To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP).


METHODS
Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CB1R) in the proximal metaphysis of left tibia.


RESULTS
At the end of the experiment, whole-body BMD in vivo in the control group [(0.156 +/- 0.008) g/cm(2)] was higher than that in the baseline group [(0.147 +/- 0.006) g/cm(2)], while the whole-body BMD in vivo [(0.147 +/- 0.006) g/cm(2)] and total BMD in vitro at femurs in the GC-treated group [(0.220 +/- 0.011) g/cm(2)] was lower than those in the control group [(0.240 +/- 0.024) g/cm(2)]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P < 0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0.05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0.05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P < 0.05).


CONCLUSIONS
The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.
Liu
Shi-Ping
SP
Institute of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Chen
Jing
J
Dai
Ru-Chun
RC
Yang
Shu-Min
SM
Li
Jian-Wei
JW
Wu
Xian-Ping
XP
Liao
Er-Yuan
EY
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013977:Tibia / Q000166:cytology / Q000378:metabolism
D005938:Glucocorticoids; D043884:Receptor, Cannabinoid, CB1