Li Haiying, Cui Yazhou, Luan Jing, Zhang Xiumei, Li Chengzhi, Zhou Xiaoyan, Shi Liang, Wang Huaxin, Han Jinxiang
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji'nan, Shandong, China; Key Laboratory for Rare Disease Research of Shandong Province, Key Laboratory for Biotech Drugs of the Ministry of Health, Shandong Medical Biotechnological Center, Shandong Academy of Medical Sciences, Ji'nan, Shandong, China.
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Science, Ji'nan, Shandong, China.
Biochem Biophys Res Commun. 2016 Feb 12;470(3):558-562. doi: 10.1016/j.bbrc.2016.01.106. Epub 2016 Jan 22.
Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a collagen-binding proteoglycan highly expressed in the developing bones. Recent studies indicated that PRELP could inhibit osteoclastogenesis as a NF-κB inhibitor. However, its role during osteoblast differentiation is still unclear. In this study, we confirmed that the expression of PRELP increased with the osteogenesis induction of preosteoblastic MC3T3-E1 cells. Down-regulation of PRELP expression by shRNA reduced ALP activity, mineralization and expression of osteogenic marker gene Runx2. Our microarray analysis data suggested that β-catenin may act as a hub gene in the PRELP-mediated gene network. We validated furtherly that PRELP knockdown could inhibit the level of connexin43, a key regulator of osteoblast differentiation by affecting β-catenin protein expression, and its nuclear translocation in MC3T3-E1 preosteoblasts. Therefore, this study established a new role of PRELP in modulating β-catenin/connexin43 pathway and osteoblast differentiation.
富含脯氨酸/精氨酸的富含亮氨酸重复序列蛋白(PRELP)是一种在发育中的骨骼中高度表达的胶原结合蛋白聚糖。最近的研究表明,PRELP作为一种NF-κB抑制剂可抑制破骨细胞生成。然而,其在成骨细胞分化过程中的作用仍不清楚。在本研究中,我们证实随着前成骨细胞MC3T3-E1细胞的成骨诱导,PRELP的表达增加。通过shRNA下调PRELP表达会降低碱性磷酸酶(ALP)活性、矿化和成骨标记基因Runx2的表达。我们的微阵列分析数据表明,β-连环蛋白可能是PRELP介导的基因网络中的枢纽基因。我们进一步验证了敲低PRELP可通过影响β-连环蛋白的蛋白表达及其在MC3T3-E1前成骨细胞中的核转位,抑制成骨细胞分化的关键调节因子连接蛋白43的水平。因此,本研究确立了PRELP在调节β-连环蛋白/连接蛋白43通路和成骨细胞分化中的新作用。