Kisspeptin 10 (human) acetate

Kisspeptin-10 (Human) (KP-10, also known as Metastin (45-54), CAS No.: 374675-21-5) is the C-terminal bioactive decapeptide corresponding to residues 45–54 of the metastasis suppressor gene product metastin, with the sequence: YNWNSFGLRF. It is a potent agonist of the G protein-coupled receptor GPR54 (also known as OT7T175, AXOR12); its Ki value for binding to GPR54 is 0.042 nM, with a binding affinity approximately 8-fold higher than that of full-length metastin. In GPR54-transfected cells, it induces calcium mobilization with an EC₅₀ of 0.18–1.1 nM, and at concentrations of 10–100 nM it can inhibit the migration of GPR54-transfected CHO cells, with potency comparable to that of full-length metastin. In the regulation of osteogenic differentiation, KP-10 activates the GPR54 receptor and upregulates gene transcription and protein expression of bone morphogenetic protein 2 (BMP2) via the NFATc4 transcription factor. Extracellularly secreted BMP2 binds to cell membrane BMP receptors in an autocrine manner, activates downstream Smad1/5/9 phosphorylation, and subsequently upregulates the expression of osteogenic marker genes such as Dlx5, Runx2, alkaline phosphatase (ALP), and osteocalcin (OC), ultimately promoting the differentiation of mesenchymal stem cells into osteoblasts and extracellular matrix mineralization. In cell experiments, 5 μM and 50 μM are commonly used to treat mouse C3H10T1/2 mesenchymal stem cells, with 50 μM being the typical working concentration. Treatment for 2 days can significantly upregulate the expression of osteogenesis-related genes, treatment for 4 days can increase ALP activity, and treatment for 20 days can induce the formation of matrix mineralization nodules.The Kisspeptin‑10–GPR54 system plays an important role in embryonic kidney development. Kisspeptin‑10/GPR54 signaling induces osteoblast differentiation by promoting BMP2 expression mediated by NFATc4.

References:

[1] Son HE, Kim KM, Kim EJ, Jang WG. Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation. Sci Rep. 2018 Feb 1;8(1):2134. doi: 10.1038/s41598-018-20571-2. PMID: 29391507; PMCID: PMC5794871.

[2] Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O, Fujino M. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001 May 31;411(6837):613-7. doi: 10.1038/35079135. PMID: 11385580.

[3] Tomita K, Niida A, Oishi S, Ohno H, Cluzeau J, Navenot JM, Wang ZX, Peiper SC, Fujii N. Structure-activity relationship study on small peptidic GPR54 agonists. Bioorg Med Chem. 2006 Nov 15;14(22):7595-603. doi: 10.1016/j.bmc.2006.07.009. Epub 2006 Aug 1. PMID: 16879969.

[4] Hori A, Honda S, Asada M, Ohtaki T, Oda K, Watanabe T, Shintani Y, Yamada T, Suenaga M, Kitada C, Onda H, Kurokawa T, Nishimura O, Fujino M. Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem Biophys Res Commun. 2001 Sep 7;286(5):958-63. doi: 10.1006/bbrc.2001.5470. PMID: 11527393.