Dexmedetomidine attenuates osteoporosis in rats

doi:10.16352/j.issn.1001-6325.2024.12.1656

Abstract

Abstract: Objective To investigate the effects of dexmedetomidine (Dex) on osteoporosis (OP) rats and possible mechanisms. Methods The rats were divided into sham operation group, osteoporosis model group (OP, replicating the OP rat model with bilateral ovariectomies), Dex-L, M, and H (Dex low, medium, and high dose treatments) groups and Dex-H+XAV-939 group (Wnt/β-catenin pathway inhibitor). Micro-CT was applied to measure bone mineral density (BMD) and bone microstructure of rat femurs. The three-point bending experiment was applied to analyze the biomechanics of the femur (maximum load, fracture deflection, elastic modulus). HE staining was applied to observe pathological changes in the femur of rats. ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP), typeⅠ procollagen amino-terminal peptide (PINP) and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ). The expression of Runx2 and Wnt3a was examined by Immunohistochemistry. Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue. Results Compared to the Sham group, the bone volume and number of trabeculae in OP group were obviously reduced, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased, CTX-Ⅰ increased (P＜0.05). Compared to the OP group, the bone trabecular structure in the Dex-L, M, and H groups was restored, the maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression all increased but CTX-Ⅰ decreased (P＜0.05). Compared to the Dex-H group, the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage. The maximum load, fracture deflection, elastic modulus, BMD, Tb.Th, Tb.N, BV/TV, ALP, PINP, Runx2, Wnt3a, β-catenin expression decreased while CTX-Ⅰ increased (P＜0.05). Conclusions Dex may antagonize OP effects by improving bone density, biomechanical properties and microstructure. The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

Key words: dexmetomidine, osteoporosis, bone microstructure, Wnt/β-catenin

CLC Number:

R580

SUN Na, SONG Linlin, CHI Jinjin, ZHONG Lulu, WANG Zhensheng, WEI Xinyun. Dexmedetomidine attenuates osteoporosis in rats[J]. Basic & Clinical Medicine, 2024, 44(12): 1656-1662.

References

[1]Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, et al. Current status of the diagnosis and management of osteoporosis[J]. Int J Mol Sci, 2022, 23:9465-9492.
[2]Amin U, McPartland A, O'Sullivan M, et al. An overview of the management of osteoporosis in the aging female population[J]. Womens Health (Lond), 2023,19:17455057231176655. doi: 10.1177/17455057231176655.
[3]García-García P, Reyes R, Évora C, et al. Osteoprotec-tive effect of the marine alkaloid norzoanthamine on an osteoporo-sis model in ovariectomized rat[J]. Biomed Pharmacother, 2022, 147:112631. doi: 10.1016/j.biopha.2022.112631.
[4]Deng S, Yu Y. Effects of dexmedetomidine as an analgesic adjuvant for surgery of femur fracture: a systematic review and meta-analysis[J]. Pharmacology, 2021, 106:453-461.
[5]Wang Z, Ge X, Wang Y, et al. Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p/VEGFA axis in postmenopausal osteoporosis[J]. Life Sci, 2021, 275:119273-119283.
[6]Marini F, Giusti F, Palmini G, et al. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders[J]. Osteoporos Int, 2023, 34:213-238.
[7]Zhang F, Attarilar S, Xie K, et al. Carfilzomib alleviated osteoporosis by targeting PSME1/2 to activate Wnt/β-catenin signaling[J]. Mol Cell Endocrinol, 2022, 540:111520. doi:10.1016/j.mce.2021.111520.
[8]Liu C, Xu R. Dexmedetomidine protects H9C2 rat cardiomyocytes against hypoxia/reoxygenation injury by regulat-ing the long non-coding RNA colon cancer-associated transcript 1/microRNA-8063/Wnt/β-catenin axis[J]. Bioengineered, 2022, 13:13300-13311.
[9]方红育, 黄涛, 周少怀, 等. 川陈皮素通过抑制STING/NF-κB信号通路促进骨质疏松大鼠的骨折愈合[J]. 免疫学杂志, 2023, 39:857-864.
[10]Lan XB, Ni YS, Liu N, et al. Neuroprotective effects of oxymatrine on hypoxic-ischemic brain damage in neonatal rats by activating the Wnt/β-catenin pathway[J]. Biomed Pharmacother, 2023, 159:114266. doi: 10.1016/j.biopha.2023.114266.
[11]向继林, 诸源江, 李曼, 等. 右美托咪定对股骨骨折模型大鼠疼痛因子及LRP5表达水平的影响[J]. 中国现代手术学杂志, 2022, 26:88-93.
[12]Kou Y, Rong X, Tang R, et al. Eldecalcitol prevented OVX-induced osteoporosis through inhibiting BMSCs senescence by regulating the SIRT1-Nrf2 signal[J]. Front Pharmacol, 2023, 14:1067085. doi: 10.1016/j.biopha.2023.114266.
[13]Xiong Y, Huang CW, Shi C, et al. Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway[J]. Exp Biol Med (Maywood), 2023, 248:2363-2380.
[14]Gu H, Wei J. Peiminine regulates bone-fat balance by canonical Wnt/β-catenin pathway in an ovariectomized rat model[J]. Phytother Res, 2023, 37:2841-2853.
[15]Liang J, Chen J, Ye Z, et al. Cathelicidin LL-37 improves bone metabolic balance in rats with ovariectomy-induced osteoporosis via the Wnt/beta-catenin pathway[J]. Physiol Res, 2022, 71:369-377.