| 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
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Mice |
RBRC02370 |
| Human and Animal Cells |
MC3T3-E1(RCB1126) |
