lncRNA TUG1 promotes proliferation and differentiation of osteoblasts by regulating the miR-545-3p/CNR2 axis

Osteoblast differentiation is an effective way to promote bone formation. Long non-coding RNA taurine upregulated 1 (TUG1) has been identified as a crucial modulator of multiple biological processes. This study was designed to investigate the function of TUG1 in the proliferation and differentiation of osteoblast precursor cells hFOB1.19. In this study, we found that TUG1 promoted hFOB1.19 cell proliferation, while TUG1 knockdown hindered cell proliferation. TUG1 and cannabinoid receptor 2 (CNR2) were upregulated, while miR-545-3p was down-regulated in hFOB1.19 cells undergoing osteoblastic differentiation. TUG1 induced osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and the expression of osteoblastic differentiation markers. TUG1 was a sponge of miR-545-3p and regulated osteoblastic differentiation by modulating miR-545-3p. Moreover, miR-545-3p directly targeted CNR2 and restored the effect of CNR2 on osteoblastic differentiation. In conclusion, TUG1 accelerated the proliferation and differentiation of osteoblasts by sponging miR-545-3p and increasing CNR2 expression, which might provide a new biomarker for bone diseases.

成骨细胞分化是促进骨形成的有效途径。长链非编码RNA牛磺酸上调基因1（TUG1）已被证实为多种生物学过程的关键调控因子。本研究旨在探究TUG1在成骨前体细胞hFOB1.19的增殖与分化中的功能。本研究发现，TUG1可促进hFOB1.19细胞增殖，而TUG1敲低则会抑制细胞增殖。在发生成骨分化的hFOB1.19细胞中，TUG1与大麻素受体2（CNR2）呈上调表达，miR-545-3p呈下调表达。TUG1可通过提升碱性磷酸酶（ALP）活性以及成骨分化标志物的表达水平，诱导成骨细胞分化。TUG1作为miR-545-3p的分子海绵，通过调控miR-545-3p参与成骨分化的调控。此外，miR-545-3p可直接靶向CNR2，并逆转CNR2对成骨分化的调控作用。综上，TUG1可通过作为miR-545-3p的分子海绵并上调CNR2表达，加速成骨细胞的增殖与分化，这一发现或可为骨相关疾病提供新型生物标志物。