载脂蛋白 D 通过 PI3K/Akt 通路减轻糖皮质激素诱导的骨髓间充质干细胞成骨抑制作用。
Apolipoprotein D alleviates glucocorticoid-induced osteogenesis suppression in bone marrow mesenchymal stem cells via the PI3K/Akt pathway.
机构信息
Department of Orthopedics, Tongren Hospital, School of Medicine, Shanghai JiaoTong University, 1111 Xianxia Road Shanghai, Shanghai, 200336, P.R. China.
出版信息
J Orthop Surg Res. 2020 Aug 8;15(1):307. doi: 10.1186/s13018-020-01824-1.
BACKGROUND
To clarify the role of apolipoprotein D (Apod) in alleviating glucocorticoid-induced osteogenesis suppression in bone marrow mesenchymal stem cells (MSCs) via the PI3K/Akt pathway, thus influencing the progression of osteoporosis (OP).
METHODS
Osteogenesis in MSCs was induced by dexamethasone (DEX) stimulation. Dynamic expressions of Apod in MSCs undergoing osteogenesis for different time points were determined by qRT-PCR. Relative levels of osteogenesis-associated genes, including ALP, RUNX2, and Osterix, in DEX-induced MSCs overexpressing Apod or not were examined. Moreover, the protein level of RUNX2, ALP, and Osterix; ALP activity; and mineralization ability influenced by Apod in osteogenic MSCs were assessed. At last, the potential influences of Apod on the PI3K/Akt pathway were identified through detecting the expression levels of PI3K and Akt in MSCs by Western blot.
RESULTS
Apod was time-dependently upregulated in MSCs undergoing osteogenesis. DEX induction downregulated ALP, RUNX2, and Osterix and attenuated ALP activity and mineralization ability in MSCs undergoing osteogenesis, which were partially reversed by overexpression of Apod. In addition, Apod overexpression upregulated the reduced levels of PI3K and Akt in DEX-induced MSCs.
CONCLUSION
Apod alleviates glucocorticoid-induced osteogenesis suppression in MSCs via the PI3K/Akt pathway, thus protecting the progression of OP.
背景
为了阐明载脂蛋白 D（Apod）通过 PI3K/Akt 通路在缓解糖皮质激素诱导的骨髓间充质干细胞（MSCs）成骨作用抑制中的作用，从而影响骨质疏松症（OP）的进展。
方法
用地塞米松（DEX）刺激诱导 MSCs 成骨。通过 qRT-PCR 确定 Apod 在经历不同时间点成骨的 MSCs 中的动态表达。检测 DEX 诱导的过表达或不表达 Apod 的 MSCs 中成骨相关基因（包括 ALP、RUNX2 和 Osterix）的相对水平。此外，评估 Apod 对成骨 MSC 中 RUNX2、ALP 和 Osterix 的蛋白水平、ALP 活性和矿化能力的影响。最后，通过 Western blot 检测 MSCs 中 PI3K 和 Akt 的表达水平，确定 Apod 对 PI3K/Akt 通路的潜在影响。
结果
Apod 在经历成骨的 MSCs 中呈时间依赖性上调。DEX 诱导下调了 ALP、RUNX2 和 Osterix，并减弱了经历成骨的 MSCs 中的 ALP 活性和矿化能力，而过表达 Apod 部分逆转了这些作用。此外，Apod 过表达上调了 DEX 诱导的 MSCs 中降低的 PI3K 和 Akt 水平。
结论
Apod 通过 PI3K/Akt 通路缓解糖皮质激素诱导的 MSCs 成骨作用抑制，从而保护 OP 的进展。
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