Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/-catenin pathway
Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/-catenin pathway
复制标题
CXCR4 的抑制通过 Wnt/-连环蛋白途径抑制强直性脊柱炎成纤维细胞的增殖和成骨潜力
DOI：
10.3892/mmr.2019.9980
复制
发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Xu, Weidong
中科院分区：
文献类型：
--
作者：
He, Chongru;Li, Dahe;Xu, Weidong
强直性脊柱炎（AS）是一种以慢性炎症和异常骨化为主要特征的自身免疫性疾病。本研究的目的是探讨C-X-C趋化因子受体4型（CXCR4）在AS患者骨化中的作用。通过western blot分析和免疫组织化学分析，对AS患者和对照组的组织进行CXCR4表达评估。分离成纤维细胞，用AMD 3100和基质细胞衍生因子-1培养，分别抑制和促进CXCR4水平。与对照组相比，AS患者髋关节滑膜组织中CXCR4表达上调。AS成纤维细胞增殖和生长速度增加。抑制CXCR4增加了-catenin的磷酸化，下调了-catenin、v-myc禽髓细胞瘤病毒癌基因同源物、cyclin D1和骨钙素的表达。茜素红染色显示抑制CXCR4后生物矿化活性降低。这些数据支持了AS患者抑制CXCR4可能抑制成纤维细胞骨化的假设。
Ankylosing spondylitis (AS) is an autoimmune condition characterized by chronic inflammation and abnormal ossification as the primary features of the disease. The aim of the present study was to investigate the role of C-X-C chemokine receptor type 4 (CXCR4) in ossification from patients with AS. CXCR4 expression was assessed by western blot analysis and immunohistochemistry analysis of tissues obtained from patients with AS and controls. Fibroblasts were isolated, cultured and incubated with AMD 3100 and stromal cell-derived factor-1 to inhibit and promote CXCR4 levels, respectively. CXCR4 was upregulated in hip synovial tissues from patients with AS compared with that observed in controls. AS fibroblasts exhibited increased proliferation and growth rates. Inhibition of CXCR4 increased the phosphorylation of -catenin and downregulated the expression of -catenin, v-myc avian myelocytomatosis viral oncogene homolog, cyclin D1 and osteocalcin. Alizarin red staining demonstrated a decrease in biomineralization activity following the inhibition of CXCR4. These data support the hypothesis that inhibiting CXCR4 in patients with AS may suppress the ossification of fibroblasts.