The effect of bone morphogenetic protein 2 intervening in iron metabolism related protein expression on rats osteoporosis by regulating hepcidin level
10.3760/cma.j.cn121113-20250221-00172
- VernacularTitle:骨形态发生蛋白2调控铁调素干预铁代谢相关蛋白表达对大鼠骨质疏松的影响
- Author:
Guo LI
1
;
Wenguang LI
;
Yingwen MA
Author Information
1. 浙江省人民医院毕节医院骨科，毕节 551700
- Publication Type:Journal Article
- Keywords:
Rats;
Osteoporosis;
Bone morphogenetic protein 2;
Hepcidins;
Osteogenesis;
Iron metabolism
- From:
Chinese Journal of Orthopaedics
2025;45(16):1072-1081
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of bone morphogenetic with protein 2 (BMP2) intervention in iron metabolism related protein expression on rats osteoporosis (OP) by regulating hepcidin level.Methods:Thirty-six 8-week-old SPF grade female SD rats with a body weight of 200-220 g were divided into sham group (Removal of adipose tissue around ovaries), model group (ovariectomy was used to prepare postmenopausal OP model rats), adenovirus group (OP model rats injected with adenovirus into the femoral cavity), and overexpression BMP2 adenovirus group (OP model rats injected with BMP2 overexpressing adenovirus into the femoral cavity) using a random number table method, with 9 rats in each group. Rats were euthanized after 2 months of injection, and femoral tissue was taken for micro computed tomography (micro-CT) three-dimensional reconstruction to observe the microstructural characteristics of bone trabeculae, and calculate bone mineral density (BMD), trabecular number (Tb.N), trabecular thickness (Tb.Th), bone volume/total volume (BV/TV), and trabecular separation (Tb.Sp) values. Hematoxylin eosin staining, Masson staining, and tartrate-resistant acid phosphatase (TRAP) staining were used to observe the pathological damage, collagen content, and osteoclast count of femoral tissues in four group rats. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), ferritin, hepcidin levels in serum were detected. Real-time quantitative PCR was used to detect BMP2 mRNA expression in femoral tissue. Western blotting were used to detect BMP2, ALP, OCN, OPN, RANKL, TRAP, CTX-I, hepcidin, FPN1, TfR1, DMT1 protein expression in femoral tissue.Results:The differences of BMD, Tb.N, Tb.Th, BV/TV, and Tb.Sp in sham group, model group, adenovirus group, and BMP2 overexpressing adenovirus group were statistically significant ( P<0.05), among them, BMD, Tb.N, Tb.Th, and BV/TV in model group were lower than those in sham group, Tb.Sp was higher than that in sham group, BMD, Tb.N, Tb.Th, and BV/TV in BMP2 overexpressing adenovirus group were higher than those in model group and adenovirus group, Tb.Sp was lower than that in model group and adenovirus group ( P<0.05). Sham group had intact bone trabeculae, abundant collagen fibers, and fewer osteoclasts in femoral tissues; Model group and adenovirus group had sparse bone trabeculae, severe loss of collagen fibers, and more osteoclasts; Bone trabeculae and collagen fibers in overexpression BMP2 adenovirus group were greater than those in model group and adenovirus group, osteoclasts were fewer than those in model group and adenovirus group. The differences of MDA, GSH, SOD, ferritin, and hepcidin in serum in four groups were statistically significant ( P<0.05), among them, MDA and ferritin in model group were higher than those in sham group, GSH, SOD, hepcidin were lower those in sham group, MDA and ferritin levels in overexpression BMP2 adenovirus group were lower those in model group and adenovirus group, GSH, SOD, hepcidin were higher than those in model group and adenovirus group ( P<0.05). BMP2 mRNA expression of femoral tissues in four groups were 1.00±0.10, 0.39±0.12, 0.39±0.08, and 3.46±0.41, respectively, BMP2 protein expression were 0.61±0.06, 0.17±0.06, 0.20±0.05, and 1.03±0.07, respectively, the differences were statistically significant ( P<0.05), among them, model group were lower those in sham group, overexpression BMP2 adenovirus group were higher than those in model group and adenovirus group ( P<0.05). The differences of ALP, OCN, OPN, RANKL, TRAP, CTX-I, hepcidin, FPN1, TfR1, and DMT1 expression of femoral tissues in sham group, model group, adenovirus group, and BMP2 overexpressing adenovirus group were statistically significant ( P<0.05), among them, ALP, OCN, OPN, and hepcidin in model group were lower than those in sham group, RANKL, TRAP, CTX-I, FPN1, TfR1, and DMT1 were higher than those in sham group, ALP, OCN, OPN, and hepcidin in BMP2 overexpressing adenovirus group were higher than those in model group and adenovirus group, RANKL, TRAP, CTX-I, FPN1, TfR1, and DMT1 were lower than those in model group and adenovirus group ( P<0.05). Conclusion:BMP2 intervention iron metabolism related protein expression promotes bone formation in OP rats by increasing hepcidin level.
