RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects
RANKL/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects
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DOI：
10.3899/jrheum.120845
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发表时间：
2013-05-01
影响因子：
3.9
通讯作者：
Cantatore, Francesco Paolo
中科院分区：
文献类型：
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作者：
Corrado, Addolorata;Neve, Anna;Cantatore, Francesco Paolo
Objective.评价Dicickopf-1蛋白因子（DICK-1）、DKK-2和β-连环蛋白（Wnt通路的组分）在人骨关节炎（OA）和骨质疏松（OP）成骨细胞中的表达，并将其与细胞代谢活性、增殖和核因子-κ B受体激活因子配体/骨保护素（RANKL/OPG）表达相关联。从健康、OA和OP供体获得原代人成骨细胞培养物。在每个细胞群中，我们评估了DICK-1、DKK-2、非磷酸化β-连环蛋白和RANKL/OPG表达、骨钙素和碱性磷酸酶（ALP）合成以及细胞增殖，包括基础条件和维生素D3刺激后。DICK-1和DICK-2在OA和OP成骨细胞中表现出相反的表达模式。OP组中RANKL/OPG比值显著较高，因为RANKL表达更高，而OA组中该比值显著较低，因为OPG表达更高。维生素D3处理增加了RANKL/OPG比值和DKIC-2表达，降低了每个细胞群中的DICK-1表达，但不影响β-连环蛋白水平。骨钙素和碱性磷酸酶的产生和细胞增殖在OA细胞中增加，而在OP细胞中减少。这些数据证实，OA和OP的特点是相反的骨变化，包括减少骨重建过程中增加成骨细胞活性的OA，和增强骨吸收活性减少成骨细胞代谢的OP，并表明，Wnt途径参与这两种疾病的发病机制。
Objective. To evaluate the expression of Dicickopf-1 protein factor (DICK-1), DKK-2, and beta-catenin, components of the Wnt pathway, in human osteoarthritic (OA) and osteoporotic (OP) osteoblasts and to correlate it to cell metabolic activity, proliferation, and receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) expression.Methods. Primary human osteoblast cultures were obtained from healthy, OA, and OP donors. In each cell population we evaluated DICK-1, DKK-2, nonphosphorylated beta-catenin and RANKL/OPG expression, osteocalcin and alkaline phosphatase (ALP) synthesis, and cell proliferation, both in basal condition and after vitamin D3 stimulation.Results. DICK-1 and DICK-2 showed opposite patterns of expression in OA and OP osteoblasts. The RANKL/OPG ratio was significantly higher in the OP group because of a greater expression of RANKL, whereas it was significantly lower in the OA group because of a higher expression of OPG. Treatment with vitamin D3 increased the RANKL/OPG ratio and DKIC-2 expression and reduced DICK-1 expression in each cell population, but did not affect beta-catenin levels. Both osteooalcin and ALP production and cell proliferation were enhanced in OA cells and reduced in the OP ones.Conclusion. These data confirm that OA and OP are characterized by opposite bone changes, consisting of reduced bone remodeling processes with increased osteoblast activity in OA, and enhanced bone resorptive activity with reduction of osteoblast metabolism in OP, and suggest that the Wnt pathway is involved in the pathogenesis of both diseases.