Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China.
Department of Rehabilitation Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China.
Differentiation. 2019 Sep-Oct;109:9-15. doi: 10.1016/j.diff.2019.07.002. Epub 2019 Jul 13.
Induction of osteoblast differentiation is an effective approach in promoting osteoblastogenesis and bone formation. MicroRNA (miR) is a kind of small regulatory RNA molecules that control both physiological and pathological processes. The purpose of this research was to explore the function of miR-187-3p in proliferation and osteogenic differentiation in human osteoblastic precursor cells (hFOB 1.19). Our results showed a significant promotion of cell proliferation by miR-187-3p in hFOB 1.19 cell accompanied by increased proliferating cell nuclear antigen (PCNA) and Ki67 expression, whereas miR-187-3p knockdown led to an inhibition of cell proliferation. Moreover, our data revealed that miR-187-3p was decreased in hFOB 1.19 cells undergoing osteoblastic differentiation. Silencing of miR-187-3p dramatically accelerated hFOB 1.19 osteoblastic differentiation, as evidenced by the increase of alkaline phosphatase (ALP) activity and calcium deposition, as well as elevated osteopontin (OPN), collagen type I alpha 1 (COL1A1), and bone sialoprotein (BSP) gene expression, whereas overexpression of miR-187-3p suppressed osteoblastic differentiation. Furthermore, we demonstrated that miR-187-3p could inhibit cannabinoid receptor type 2 (CNR2) expression by targeting its 3' untranslated region (UTR). Upregulation of CNR2 inversed the inhibiting influence of miR-187-3p on hFOB 1.19 osteogenic differentiation. Collectively, our results showed a pivotal role of miR-187-3p/CNR2 axis in osteoblastic differentiation, indicating that miR-187-3p may serve as a promising target in the therapy of osteoporosis.
成骨细胞分化的诱导是促进成骨细胞生成和骨形成的有效方法。miRNA（miR）是一种小的调节 RNA 分子，可控制生理和病理过程。本研究旨在探讨 miR-187-3p 在人成骨前体细胞（hFOB 1.19）增殖和成骨分化中的作用。我们的结果表明，miR-187-3p 可显著促进 hFOB 1.19 细胞的增殖，同时伴随着增殖细胞核抗原（PCNA）和 Ki67 表达的增加，而 miR-187-3p 敲低则导致细胞增殖受到抑制。此外，我们的数据显示，miR-187-3p 在 hFOB 1.19 细胞成骨分化过程中减少。miR-187-3p 沉默显著加速 hFOB 1.19 成骨分化，碱性磷酸酶（ALP）活性和钙沉积增加，骨桥蛋白（OPN）、I 型胶原α 1 链（COL1A1）和骨涎蛋白（BSP）基因表达水平升高，而过表达 miR-187-3p 则抑制成骨分化。此外，我们证明 miR-187-3p 可以通过靶向其 3'非翻译区（UTR）抑制大麻素受体 2（CNR2）的表达。CNR2 的上调逆转了 miR-187-3p 对 hFOB 1.19 成骨分化的抑制作用。综上所述，miR-187-3p/CNR2 轴在成骨分化中起关键作用，表明 miR-187-3p 可能成为骨质疏松症治疗的有前途的靶点。
