cAMP/PKA/CREB信号通路对卵巢早衰继发骨质疏松大鼠骨微结构影响研究

doi:10.13418/j.issn.1001-165x.2024.4.13

Abstract

Abstract: Objective To explore cyclicadenosine monophosphate (cAMP)/ protein kinase A(PKA)/cAMP response element binding effect of proteins protein, CREB) signaling pathway in the process of osteoporosis secondary to premature ovarian failure on bone microstructure and bone marrow mesenchymal stem cells mineralized nodules activity in rats. Methods Bioinformatics methods were used to analyze the cAMP/PKA/CREB signaling pathway. The model of osteoporosis secondary to premature ovarian failure was established by intraperitoneal injection of cyclophosphamide (50mg/kg for the first time, followed by 8mg/kg for two weeks) in adult female rats. At the same time, the normal saline group and the aged group were set as controls, and 1mg/kg PKA inhibitor H89 was injected intraperitoneally for two weeks after modeling. The femoral head and condyle were stained with HE and Safranin fast green. The bone marrow mesenchymal stem cells of the three groups were stained with osteogenic induction alizarin red. Results Cyclophosphamide successfully induced osteoporosis secondary to premature ovarian failure in female rats. When PKA was inhibited, the activity of bone mineralized nodules of stem cells was significantly decreased, and the bone microstructure of the three groups was significantly decreased, mainly in the epiphysis, the cartilage proliferation area and cartilage calcification area of the epiphyseal plate, and the trabecular bone, especially in the saline group. Conclusions The cAMP/PKA/CREB signaling pathway plays an important role in regulating the physiological activities of ovarian granulosa cells, osteogenic differentiation and cartilage growth. Inhibition of PKA significantly decreases the bone microstructure in rats.

Key words: cAMP/PKA/CREB; , Osteoporosis secondary to premature ovarian failure; , Bone microstructure

CLC Number:

R681

Zhang Yanru, Yang Yue, Dong Jiaqi, Xu Jiingchao, Han Daozheng, Su Jiazi. Effect of cAMP/PKA/CREB signaling pathway on bone microstructure in rats with osteoporosis secondary to premature ovarian failure[J]. Chinese Journal of Clinical Anatomy, 2024, 42(4): 435-442.

References

[1] Jankowska K. Premature ovarian failure[J]. Prz Menopauzalny, 2017, 16(2):51-56. DOI： 10.5114/pm.2017.68592.
[2] Kim JY, Ohn J, Yoon JS, et al. Priming mobilization of hair follicle stem cells triggers permanent loss of regeneration after alkylating chemotherapy[J].Nat Commun, 2019, 10(1):1-16. DOI: 10.1038/s41467-019-11665-0.
[3] Deng J, Zhong YF, Wu YP, et al. Carnosine attenuates cyclopho sphamide-induced bone marrow suppression by reducing oxidative DNA damage[J]. Redox Biol, 2018,(14):1-6. DOI: 10.1016/j.redox. 2017.08.003.
[4] Zou Z, Chen Y, Shen Q, et al. Neural plasticity associated with hippocampal PKA-CREB and NMDA signaling is involved in the antidepressant effect of repeated low dose of Yueju Pill on chronic mouse model of learned helplessness[J]. Neural Plast, 2017:1-11.DOI: 10.1155/2017/9160515.
[5] Jin Y, Liu Q, Chen P, et al. A novel prostaglandin E receptor 4 (EP4) small molecule antagonist induces articular cartilage regeneration[J]. Cell Discov. 2022, 8(1):1-22. DOI: 10.1038/s41421-022-00382-6.
[6] Cai X, Fu H, Wang Y, et al. Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro[J]. J Ovarian Res, 2020, 13(1):1-10. DOI: 10.1186/s13048-020-00740-6.
[7] Zhang H, Kong Q, Wang J, et al. Complex roles of cAMP-PKA-CREB signaling in cancer[J]. Exp Hematol Oncol, 2020,9(1):1-13. DOI: 10.1186/s40164-020-00191-1.
[8] Luo Y, Kuang S, Li H, et al. cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress[J].Oncotarget, 2017, 8(22):35558-35572. DOI: 10.18632/oncotarget. 16009.
[9] 张玉林, 邹姮, 张觇宇. 环磷酰胺诱导大鼠卵巢功能不全及差异表达基因分析[J].基础医学与临床, 2022, 42(8):1243-1249. DOI: 10.16352/j.issn.1001-6325.2022.08.1243
[10] Cai YJ, Ren LN, Tan SW, et al. Mechanism, diagnosis, and treatment of cyclic Cushing's syndrome: A review[J].Biomed Pharmacother, 2022, 153:1-10. DOI: 10.1016/j.biopha.2022.113301.
[11] Krysiak R, Kedzia A, Okopień B. Cyclic Cushing's syndrome[J]. Acta Clin Belg, 2012, 67(1):30-33. DOI: 10.2143/ACB.67.1.2062623.
[12]Checchi S, Brilli L, Guarino E, et al. Cyclic Cushing's disease with paradoxical response to dexamethasone[J]. J Endocrinol Invest, 2005, 28(8):741-745. DOI: 10.1007/BF03347559.
[13] 余元勋, 尚希福, 何光远, 等.中国分子骨质疏松症学 [M] .安徽：安徽科学技术出版社，2016:111-112.
[14] Riggs BL. The mechanisms of estrogen regulation of bone resorption[J]. J Clin Invest, 2000, 106(10):1203-1204. DOI:10.1172/JCI11468.
[15] Goswami D, Conway GS. Premature ovarian failure[J]. Horm Res, 2007, 68(4):196-202. DOI: 10.1159/000102537.
[16] Kimple ME, Keller MP, Rabaglia MR, et al. Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion[J]. Diabetes, 2013, 62(6):1904-1912.DOI: 10.2337/db12-0769.
[17]Khannpnavar B, Mehta V, Chao Qi, et al. Structure and function of adenylyl cyclases, key enzymes in cellular signaling[J].Curr Opin Struct Biol, 2020, 63:34-41. DOI: 10.1016/j.sbi.2020.03.003.
[18]Chen B, Lin T, Yang X, et al. Intermittent parathyroid hormone (1-34) application regulates cAMP-response element binding protein activity to promote the proliferation and osteogenic differentiation of bone mesenchymal stromal cells, via the cAMP/PKA signaling pathway[J]. Exp Ther Med, 2016, 11(6):2399-2406. DOI: 10.3892/etm.2016.3177.
[19]Boutin A, Neumann S, Gershengorn MC. Multiple transduction pathways mediate thyrotropin Receptor signaling in preosteoblast-like cells[J]. Endocrinology, 2016,157(5):2173-2181.DOI: 10.1210/en.2015-2040.
[20] Gesty-Palmer D, Chen M, Reiter E, et al. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation[J]. J Biol Chem, 2006, 281(16):10856-10864. DOI: 10.1074/jbc.M513380200.
[21] Sun L, Vukicevic S, Baliram R, et al. Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss[J]. Proc Natl Acad Sci U S A, 2008,105(11):4289-4294.DOI: 10.1073/pnas.0712395105.
[22] Hirota K, Hirashima T, Horikawa K, et al. C-type natriuretic peptide-induced PKA activation promotes endochondral bone formation in hypertrophic chondrocytes[J]. Endocrinology, 2022, 163(3):1-12. DOI: 10.1210/endocr/bqac005.
[23] Zeng C, Wang S, Chen F, et al. Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in BMSCs by triggering autophagy via PKA/mTOR/ULK1 signaling[J]. Phytother Res, 2023, 37(1):252-270.DOI: 10.1002/ptr.7610.
[24] Liu X, Ouyang L, Chen L, et al. Hydroxyapatite composited PEEK with 3D porous surface enhances osteoblast differentiation through mediating NO by macrophage[J]. Regen Biomater, 2021, 9:1-12. DOI: 10.1093/rb/rbab076.
[25] Chen M, Cui Y, Li H, et al. Icariin promotes the osteogenic action of BMP2 by Activating the cAMP signaling pathway[J]. Molecules, 2019, 24(21):1-16. DOI: 10.3390/molecules24213875.
[26] Kaseder M, Schmid N, Eubler K, et al. Evidence of a role for cAMP in mitochondrial regulation in ovarian granulosa cells[J]. Mol Hum Reprod, 2022, 28(10):1-12. DOI: 10.1093/molehr/gaac030.
[27] Armouti M, Rodriguez-Esquivel M, Stocco C. Mechanism of negative modulation of FSH signaling by salt-inducible kinases in rat granulosa cells[J]. Front Endocrinol (Lausanne), 2022, 13:1-12. DOI: 10.3389/fendo.2022.1026358.
[28]Liu Y, Zhong Y, Shen X, et al. Luteinizing hormone stimulates the expression of amphiregulin in human theca cells[J]. J Ovarian Res, 2022, 15(1):1-10. DOI: 10.1186/s13048-022-01062-5.
[29] Wu H, Sun P, Lv C, et al. Effects of IL-11/IL-11 Receptor Alpha on Proliferation and Steroidogenesis in Ovarian Granulosa Cells of Dairy Cows[J]. Cells, 2023, 12(4):1-17. DOI: 10.3390/cells12040673.

Effect of cAMP/PKA/CREB signaling pathway on bone microstructure in rats with osteoporosis secondary to premature ovarian failure

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