RRC ID 71624
著者 Sasaki Y, Nakatsuka R, Inouchi T, Masutani M, Nozaki T.
タイトル Inhibition of Poly (ADP-Ribose) Glycohydrolase Accelerates Osteoblast Differentiation in Preosteoblastic MC3T3-E1 Cells.
ジャーナル Int J Mol Sci
Abstract Poly ADP-ribosylation (PARylation) is a post-translational modification catalyzed by poly (ADP-ribose) polymerase (PARP) family proteins such as PARP1. Although PARylation regulates important biological phenomena such as DNA repair, chromatin regulation, and cell death, little is known about the relationship between osteoblast differentiation and the PARylation cycle involving PARP1 and the poly (ADP-ribose)-degrading enzyme poly (ADP-ribose) glycohydrolase (PARG). Here, we examined the effects of PARP inhibitor olaparib, an approved anti-cancer agent, and PARG inhibitor PDD00017273 on osteoblast differentiation. Olaparib decreased alkaline phosphatase (ALP) activity and suppressed mineralized nodule formation evaluated by Alizarin Red S staining in preosteoblastic MC3T3-E1 cells, while PDD00017273 promoted ALP activity and mineralization. Furthermore, PDD00017273 up-regulated the mRNA expression levels of osteocalcin and bone sialoprotein, as osteoblast differentiation markers, and osterix as transcription inducers for osteoblast differentiation, whereas olaparib down-regulated the expression of these genes. These findings suggest that PARG inhibition by PDD00017273 accelerates osteoblast differentiation in MC3T3-E1 cells. Thus, PARG inhibitor administration could provide therapeutic benefits for metabolic bone diseases such as osteoporosis.
巻・号 23(9)
公開日 2022-5-2
DOI 10.3390/ijms23095041
PII ijms23095041
PMID 35563432
PMC PMC9103302
MeSH Adenosine Diphosphate Glycoside Hydrolases / metabolism Osteoblasts / metabolism Poly (ADP-Ribose) Polymerase-1 / genetics Poly Adenosine Diphosphate Ribose / metabolism Poly(ADP-ribose) Polymerases* / metabolism Ribose*
IF 4.556
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)