RRC ID 34569
Author Noguchi T, Ebina K, Hirao M, Kawase R, Ohama T, Yamashita S, Morimoto T, Koizumi K, Kitaguchi K, Matsuoka H, Kaneshiro S, Yoshikawa H.
Title Progranulin plays crucial roles in preserving bone mass by inhibiting TNF-α-induced osteoclastogenesis and promoting osteoblastic differentiation in mice.
Journal Biochem Biophys Res Commun
Abstract A close correlation between atherosclerosis, inflammation, and osteoporosis has been recognized, although the precise mechanism remains unclear. The growth factor progranulin (PGRN) is expressed in various cells such as macrophages, leukocytes, and chondrocytes. PGRN plays critical roles in a variety of diseases, such as atherosclerosis and arthritis by inhibiting Tumor Necrosis Factor-α (TNF-α) signaling. The purpose of this study was to investigate the effect of PGRN on bone metabolism. Forty-eight-week old female homozygous PGRN knockout mice (PGRN-KO) (n = 8) demonstrated severe low bone mass in the distal femur compared to age- and sex-matched wild type C57BL/6J mice (WT) (n = 8) [BV/TV (%): 5.8 vs. 16.6; p < 0.001, trabecular number (1/mm): 1.6 vs. 3.8; p < 0.001]. In vitro, PGRN inhibited TNF-α-induced osteoclastogenesis from spleen cells of PGRN-KO mice. Moreover, PGRN significantly promoted ALP activity, osteoblast-related mRNA (ALP, osteocalcin) expression in a dose-dependent manner and up-regulated osteoblastic differentiation by down-regulating phosphorylation of ERK1/2 in mouse calvarial cells. In conclusion, PGRN may be a promising treatment target for both atherosclerosis and inflammation-related osteoporosis.
Volume 465(3)
Pages 638-43
Published 2015-9-25
DOI 10.1016/j.bbrc.2015.08.077
PII S0006-291X(15)30467-8
PMID 26297947
MeSH Animals Bone Resorption / chemically induced Bone Resorption / diagnostic imaging Bone Resorption / metabolism* Cell Differentiation Female Femur / diagnostic imaging Femur / metabolism* Granulins Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* MAP Kinase Signaling System Mice Mice, Inbred C57BL Mice, Knockout Osteoblasts / diagnostic imaging Osteoblasts / metabolism* Osteoblasts / pathology Osteogenesis* Progranulins Radiography Tumor Necrosis Factor-alpha
IF 2.985
Times Cited 18
Mice RBRC02370
Human and Animal Cells MC3T3-E1(RCB1126)