title: 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.affiliation: Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, 410011 Hunan, People's Republic of China.
authors.forename: You-Shuo
authors.initials: YS
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao