Association of serum Dkk-1 levels with β-catenin in patients with postmenopausal osteoporosis

Abstract

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group (P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin (r=-0.161, P=0.003) and OPG (r=-0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin (β=-0.165, P=0.009) and BMD (β=-0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX (β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis

“…The neurons were also treated with inhibitors or activators of Wnt signaling, and the inhibitors/activators were co-incubated with the corresponding Wnt ligand. The inhibitors of canonical Wnt signaling that were used included Dickkopf 1 (Dkk1, 30 ng/ml; an agonist of Wnt ligands) (83) and TCS183 (300 M; a peptide used as a competitive inhibitor of GSK-3␤ (Ser 9 ) phosphorylation) (84,85). We used LiCl (10 mM, which is a classic inhibitor of GSK-3␤) as an activator of canonical Wnt signaling (86,87).…”

L-securinine inhibits the proliferation of A549 lung cancer cells and promotes DKK1 promoter methylation

“…A previous meta-analysis revealed that DKK1 is a potential biomarker for lung cancer diagnosis (34). It has previously been reported that DKK1, as a secreted protein with two cysteine rich regions, negatively regulates the Wnt signaling pathway (35).…”

<p>Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update</p>

“…Numerous studies focusing on sclerostin has been reviewed by Garnero et al, 54 having shown that serum sclerostin levels are increased in patients with a high risk of osteoporosis. Tian et al 55 found a significant increase in serum DKK-1 levels in patients with postmenopausal osteoporosis in comparison with the age-paired control group. Intriguing insights into bone remodeling processes during osteoporosis have been disclosed by Ueland et al 56 According to their findings, both sclerostin and DKK-1 are incorporated in the bone mass under normal Wnt signaling; during menopausal imbalance, these proteins are unsynchronized released in the bone matrix further promoting bone resorption.…”