Connective tissue growth factor is a downstream mediator for preptin-induced proliferation and differentiation in human osteoblasts.

Abstract

Preptin, a newly isolated 34-amino-acid peptide hormone that is cosecreted with insulin and amylin from pancreatic beta-cells, has emerged as a regulatory element in bone metabolism, but its mechanism remains unclear. We assessed the effects of preptin on proliferation and differentiation of human osteoblasts and investigated the mechanism involved. Our results demonstrated that preptin promoted human osteoblasts proliferation and alkaline phosphatase activity. Suppression of connective tissue growth factor (CTGF), which was upregulated by preptin in a dose- and time-dependent manner, with small interfering RNA (siRNA) abolished the preptin-induced human osteoblasts proliferation and differentiation. Preptin induced activation of ERK mitogen-activated protein kinase (MAPK), but not p38 or JNK in human osteoblasts. Furthermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion and blocked the promoting effect of preptin on osteoblasts proliferation and differentiation. These data demonstrated that preptin is involved in bone anabolism mediated by ERK/CTGF in human osteoblasts and may contribute to the preservation of bone mass observed in hyperinsulinemic states, such as obesity.

• Authors: You-Shuo Liu, Ying Lu, Wei Liu, Hui Xie, Xiang-Hang Luo, Xian-Ping Wu, Ling-Qing Yuan, Er-Yuan Liao
• Journal: Amino acids (Amino Acids) Vol. 38 Issue 3 Pg. 763-9 (Mar 2010) ISSN: 1438-2199 [Electronic] Austria
• PMID: 19333718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCN2 protein, human
• Peptide Fragments
• RNA, Small Interfering
• Recombinant Proteins
• preptin
• Connective Tissue Growth Factor
• Insulin-Like Growth Factor II
• Extracellular Signal-Regulated MAP Kinases
• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (metabolism)
• Bone and Bones (cytology, metabolism)
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Connective Tissue Growth Factor (genetics, metabolism)
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Humans
• Insulin-Like Growth Factor II (pharmacology, physiology)
• Osteoblasts (cytology, enzymology, metabolism, physiology)
• Peptide Fragments (pharmacology, physiology)
• Phosphorylation
• RNA, Small Interfering
• Recombinant Proteins
• Signal Transduction
• Time Factors
• Up-Regulation