Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation

Abstract

Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5). In the present study, KP-10-treatment significantly increased the expression of osteogenic genes, including mRNA and protein levels of BMP2, in C3H10T1/2 cells. Moreover, KP-10 induced BMP2-luc activity and increased phosphorylation of Smad1/5/9. In addition, NFATc4 specifically mediated KP-10-induced BMP2 gene expression. However, KP-10 treatment did not induce expression of the BMP2 and Runx2 genes in GPR54−/− cells. To examine whether KP-10 induced secretion of BMP2 to the culture medium, we used the conditioned-medium (C.M) of KP-10 treated medium on C3H10T1/2 cells. Dlx5 and Runx2 expressions were higher in GPR54−/− cells treated with C.M than in those treated with KP-10. These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.

Cip2A modulates osteogenic differentiation via the ERK‐Runx2 pathway in MG63 cells

“…MG63 cells were transiently transfected with the indicated plasmids using Lipofectamine 2000 (Invitrogen, Carlsbad, CA), as described previously 37 . Cells were harvested 24 h after transfection.…”

MicroRNA-197-3p Inhibits the Osteogenic Differentiation in Osteoporosis by Down-Regulating KLF 10

“…Studies have found that miR-17, miR-27a, miR-140-5p and miR-654-5p can directly inhibit the expression of BMP2 to regulate osteogenic differentiation. 34 MiR-197-3p, as a member of miRNA family, can regulate the proliferation of tumor cells. 35 In this study, it was found that the expression of miR-197-3p in OVX group was increased.…”

Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

“…Kisspeptin-10 (Kp-10) is a peptide hormone encoded by kiss 1 gene, which is synthesized by hydropthalamic neurons and play a variety of biological functions in the body through its receptor GPR54 [16]. Meanwhile, GPR54 regulates the release of GnRH and inhibits the synthesis of growth hormone [17,18].…”