Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.

骨质疏松症的特征是骨矿物质密度降低和骨骼质量下降，这导致骨折的高风险。一些微RNA（miRNA）已被确认为成骨细胞分化以维持骨量维持的潜在调节剂。我们旨在阐明miR-122是否可以调节卵巢切除的骨质疏松大鼠的成骨细胞分化。在切除卵巢的大鼠中，miR-122上调，而Purkinje细胞蛋白4（PCP4）下调。通过双荧光素酶报告基因测定，PCP4被鉴定为miR-122的靶标。我们用miR-122模拟或抑制剂或PCP4过表达载体转染了来自卵巢切除大鼠的分离的成骨细胞。miR-122的过表达抑制成骨细胞的增殖和分化，而PCP4的过表达促进成骨细胞的增殖和分化。miR-122可以诱导c-Jun NH2末端激酶（JNK）信号传导途径的激活，而PCP4可以阻止该途径。救援实验进一步证明，miR-122对成骨细胞分化的抑制作用可以通过激活PCP4或抑制JNK信号通路来补偿。总的来说，我们的数据暗示miR-122抑制骨质疏松大鼠的成骨细胞增殖和分化，突出了骨质疏松患者的新型治疗靶点。