|
|
Effect of ursolic acid derivatives on bone remodeling in diabetic osteoporosis |
ZHAO Yuqin1, ZHANG Chengjie1, XIANG Shufang2, |
1 Department of Emergency, Binzhou People's Hospital, Binzhou 256610,P.R.China; 2 Department of Obstetrics, Binzhou People's Hospital |
|
|
Abstract Objective The aim of this study was to investigate the effects of ursolic acid derivatives (UAD) on bone remodeling in diabetic osteoporosis. Methods The mice were randomly divided into three groups: control group, STZ group and US group.The tibia was taken for gene and protein expression determination and histomorphologicalanalysis. Bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and bone mineral density/total volume (BMD/TV) were measured.Detection of osteoprotegerin/nuclear factor-kappa B receptor activator (OPG/RANKL) ratio and expression of key regulators of bone metabolism. Results Compared with the control group, OPG/RANKL ratio and OPG in STZ group decreased significantly and RANKL increased significantly.The OPG/RANKL ratio increased significantly in US group.The expression of MMP9 and CAI in STZ group was significantly higher than that in control group, while the expression of Runx2 and TGF-beta in STZ group was significantly lower than that in control group.US group reversed the expression of MMP9, CAII, RUNX2 and TGF-beta in diabetic mice at the same time. Conclusion UAD reverses STZ-induced trabecular bone injury by promoting osteoblast differentiation, new bone formation and inhibiting osteoclast bone resorption.
|
Received: 13 May 2019
|
|
|
|
|
[1] 曾晓燕,吴斌,杨慧英,等.血清OPG/RANKL与云南地区2型糖尿病性骨质疏松症的相关性[J]. 昆明医科大学学报,2017,38(2):82-85. [2] 孟艳秋,李思竹.熊果酸衍生物的合成及抗肿瘤活性的研究[J]. 药学研究,2016,35(9):514-516. [3] 孟庆国,王朝明,王文智,等.熊果酸衍生物的合成与活性研究进展[J]. 济宁医学院学报,2017,40(4):245-255. [4] 张松菁,严孙杰,杨立勇,等.骨密度与高血压、糖脂代谢紊乱的相关性[J].中华高血压杂志,2018,26(3):241-247. [5] 吕芳,李梅.骨质疏松症靶向治疗药物[J].中华骨质疏松和骨矿盐疾病杂志,2017,10(6):566-571. [6] Wang W, Olson D, Liang G, et al. Collagen XXIV (Col24alpha1) promotes osteoblastic differentiation and mineralization through TGF-beta/ Smads signaling pathway[J]. Int J Biol Sci,2012,8(10):1310-1322. [7] Pater A, Sypniewska G, Pilecki O. Biochemical markers of bone cell activity in childrenwithtype 1 dia-betesmellitus[J]. J PediatrEndocrinol Metab,2010,23(1-2):81-86. [8] Zhang Z, Song C, Fu X, et al. High-dose diosgenin re-duces bone loss in ovariectomized rats via attenuation of the RANKL/OPG ratio[J]. Int J Mol Sci,2014,15(9): 17130-17147. [9] Loureiro M B, Ururahy M A, Freire-Neto F P, et al. Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes[J]. Diabetes Res Clin Pract,2014,103(3):452-457. [10] Xiang G D, Sun H L, Zhao L S. Changes of osteoprotegerin before and after insulin therapy in type 1 dia-beticpatients[J]. Diabetes Res Clin Pract,2007,76(2):199-206. [11] Touaitahuata H, Cres G, de Rossi S, et al. The mineral dissolution function of osteoclasts is dispensable for hypertrophic cartilage degradation during long bone development and growth[J]. Dev Biol,2014, 393(1): 57-70. [12] Tanaka H, Tanabe N, Kawato T, et al. Nico-tine affects bone resorption and suppresses the expression of cathepsin K, MMP-9 and vacuolar-type H(+)-ATP ase d2 and actin organization in osteoclasts[J]. PLoS One,2013,8(3): 59402. [13] Kartner N, Manolson M F. Novel techniques in the development of osteoporosis drug therapy:theosteo-clast ruffled-border vacuolar H(+)- ATPase as an emerging target[J]. Expert Opin Drug Discov,2014,9(5):505-522. [14] Claros S, Rico-Llanos G A, Becerra J, et al. A novel human TGF-beta1fusion protein in combina-tion with rhBMP-2 increases chondro-osteogenic differentiation of bone marrow mesenchymal stem cells[J]. Int J Mol Sci,2014,15(7):11255-11274. |
|
|
|