Home
Resources
Publications
K6PC-5, a Novel Sphingosine Kinase 1 (SphK1) Activator, Alleviates Dexamethasone-Induced Damages to Osteoblasts Through Activating SphK1-Akt Signaling

K6PC-5, a Novel Sphingosine Kinase 1 (SphK1) Activator, Alleviates Dexamethasone-Induced Damages to Osteoblasts Through Activating SphK1-Akt Signaling

Feng Ji, Li Mao, Yuanyuan Liu, Xiaojian Cao, Yue Xie, Shouguo Wang, Haodong Fei

Biochem Biophys Res Commun. 2015 Mar 13;458(3):568-575.

PMID: 25680461

Abstract:

Long-term glucocorticoid usage is a common cause of non-traumatic femoral head osteonecrosis. Glucocorticoids (i.e. dexamethasone (Dex)) could directly induce damages to osteoblasts. In the current study, we investigated the potential activity of K6PC-5 [N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide], a novel sphingosine kinase 1 (SphK1) activator, against this process. Our data revealed that both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts were responsible to K6PC-5. K6PC-5 activated SphK1, increased sphingosine-1-phosphate (S1P) production and induced Akt phosphorylation in cultured osteoblasts. Functionally, K6PC-5 protected osteoblasts from Dex-induced apoptosis and necrosis. Such signaling and functional effects by K6PC-5 were prevented by the SphK1 inhibitor N,N-dimethylsphingosine (DMS), and by SphK1-siRNAs. On the other hand, exogenously-added S1P activated Akt and reduced Dex-induced osteoblast damages. LY294002 and MK-2206, two established Akt inhibitors, alleviated K6PC-5- or S1P-mediated osteoblast protection against Dex. Together, our results suggest that K6PC-5 alleviates Dex-induced osteoblast injuries through activating SphK1-Akt signaling. K6PC-5 might be further investigated in animal or clinical studies for its anti-glucocorticoids-associated osteonecrosis potential.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP756875511	K6PC-5		756875-51-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: