Role and mechanism of dexmedetomidine in regulating bone metabolism in tail-suspended osteoporotic rats

‍Objective‍ ‍To investigate the effect of dexmedetomidine (Dex) on bone loss in tail-suspended rats and primarily explore its regulatory mechanism on bone metabolism. Methods‍ ‍A total of 30 male rats were randomly divided into a control group, a model group, and a Dex group, with 10 animals in eac...

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Main Authors: GUO Yunliang, WANG Can, ZHANG Xinyu
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2025-02-01
Series:陆军军医大学学报
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Online Access:https://aammt.tmmu.edu.cn/html/202408018.html
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Summary:‍Objective‍ ‍To investigate the effect of dexmedetomidine (Dex) on bone loss in tail-suspended rats and primarily explore its regulatory mechanism on bone metabolism. Methods‍ ‍A total of 30 male rats were randomly divided into a control group, a model group, and a Dex group, with 10 animals in each group. Rat model of osteoporosis was established by hind limb suspension for 4 weeks. Dex at a dose of 10 μg/kg was given intraperitoneally, once every other day from the day of tail suspension. And equal amount of normal saline was given to the control and model group. Bone histological staining was used to observe the trabecular bone area fraction. Biomechanical three-point bending test was employed to measure the maximum load, stiffness, and fracture energy. Dual calcein/alizarin red fluorescence labeling and tartrate resistant acid phosphatase (TRAP) staining were applied respectively to detect the mineral apposition rate and bone formation rate as well as the number of osteoclasts on bone surfaces. Secondly, after primary osteoblasts were isolated from the tibiae of tail-suspended rats and then treated with 1 nmol/L Dex, the proportion of alkaline phosphatase (ALP)-positive osteoblasts and the activity of the enzyme were detected by ALP staining and activity test. qRT-PCR was applied to measure the expression of osteogenic activity-related factors, including osteocalcin (Ocn), Runt related transcription factor 2 (Runx2), Osterix protein (Osx), and type 1 collagen (Col1). Results‍ ‍The animal experiments revealed that Dex treatment significantly increased the tibial trabecular bone area fraction, inhibited the decrease in bone mechanical strength, and enhanced the mineralization deposition rate and new bone formation rate of trabecular bone in the tail-suspended rats (all P<0.001). The in vitro experiments showed that Dex treatment obviously improved ALP activity and the number of ALP-positive osteoblasts in primary osteoblasts isolated from tail-suspended rats (P<0.01), and up-regulated the expression levels of osteogenic differentiation-related genes, such as Ocn, Runx2, Osx and Col1 (P<0.01). Conclusion‍ ‍Dex exerts anti-bone loss effect in tail-suspended rats, which may be associated with its stimulation on osteoblast-mediated bone formation.
ISSN:2097-0927