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

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

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Chinese Journal of Clinical Anatomy ›› 2024, Vol. 42 ›› Issue (4) : 435-442. DOI: 10.13418/j.issn.1001-165x.2024.4.13

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

Zhang Yanru¹, Yang Yue², Dong Jiaqi², Xu Jiingchao², Han Daozheng², Su Jiazi²

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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.

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cAMP/PKA/CREB; / Osteoporosis secondary to premature ovarian failure; / Bone microstructure

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

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