Osteoporosis (OP) is the most common systematic bone disorder among elderly individuals worldwide. Long noncoding RNAs (lncRNAs) are involved in biological processes in various human diseases. It has been previously revealed that PAX8 antisense RNA 1 (PAX8-AS1) is upregulated in OP. However, its molecular mechanism in OP remains unclear. Therefore, we specifically designed this study to determine the specific role of PAX8-AS1 in OP. We first established a rat model of OP and then detected PAX8-AS1 expression in the rats with RT-qPCR. Next, to explore the biological function of PAX8-AS1 in osteoblasts, in vitro experiments, such as Cell Counting Kit-8 (CCK-8) assays, flow cytometry, western blotting and immunofluorescence (IF) staining, were conducted. Subsequently, we performed bioinformatic analysis and luciferase reporter assays to predict and identify the relationships between microRNA 1252-5p (miR-1252-5p) and both PAX8-AS1 and G protein subunit beta 1 (GNB1). Additionally, rescue assays in osteoblasts clarified the regulatory network of the PAX8-AS1/miR-1252-5p/GNB1 axis. Finally, in vivo loss-of-function studies verified the role of PAX8-AS1 in OP progression. The results illustrated that PAX8-AS1 was upregulated in the proximal tibia of OP rats. PAX8-AS1 silencing promoted the viability and inhibited the apoptosis and autophagy of osteoblasts. PAX8-AS1 interacted with miR-1252-5p. GNB1 was negatively regulated by miR-1252-5p. In addition, the impacts of PAX8-AS1 knockdown on osteoblasts were counteracted by GNB1 overexpression. PAX8-AS1 depletion suppressed OP progression by inhibiting apoptosis and autophagy in osteoblasts. In summary, PAX8-AS1 suppressed the viability and activated the autophagy of osteoblasts via the miR-1252-5p/GNB1 axis in OP.

骨质疏松症（OP）是全世界老年人中最常见的系统性骨病。长非编码RNA (lncRNA) 参与多种人类疾病的生物过程。此前已有研究表明，PAX8 反义 RNA 1 (PAX8-AS1) 在 OP 中表达上调。然而，其在OP中的分子机制仍不清楚。因此，我们专门设计了本研究来确定PAX8-AS1在OP中的具体作用。我们首先建立OP大鼠模型，然后通过RT-qPCR检测大鼠中PAX8-AS1的表达。接下来，为了探索PAX8-AS1在成骨细胞中的生物学功能，进行了细胞计数试剂盒8（CCK-8）测定、流式细胞术、蛋白质印迹和免疫荧光（IF）染色等体外实验。随后，我们进行了生物信息学分析和荧光素酶报告基因检测，以预测和鉴定 microRNA 1252-5p (miR-1252-5p) 与 PAX8-AS1 和 G 蛋白亚基 beta 1 (GNB1) 之间的关系。此外，成骨细胞的救援实验阐明了 PAX8-AS1/miR-1252-5p/GNB1 轴的调控网络。最后，体内功能丧失研究验证了 PAX8-AS1 在 OP 进展中的作用。结果表明，OP 大鼠胫骨近端中 PAX8-AS1 表达上调。PAX8-AS1沉默可促进成骨细胞的活力并抑制其凋亡和自噬。PAX8-AS1 与 miR-1252-5p 相互作用。GNB1 受到 miR-1252-5p 的负调控。此外，PAX8-AS1 敲低对成骨细胞的影响被 GNB1 过表达所抵消。PAX8-AS1 缺失通过抑制成骨细胞的凋亡和自噬来抑制 OP 进展。总之，PAX8-AS1 通过 OP 中的 miR-1252-5p/GNB1 轴抑制成骨细胞的活力并激活成骨细胞的自噬。