| RRC ID |
78819
|
| Author |
Takami K, Okamoto K, Etani Y, Hirao M, Miyama A, Okamura G, Goshima A, Miura T, Kurihara T, Fukuda Y, Kanamoto T, Nakata K, Okada S, Ebina K.
|
| Title |
Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.
|
| Journal |
JCI Insight
|
| Abstract |
NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.
|
| Volume |
8(22)
|
| Published |
2023-11-22
|
| DOI |
10.1172/jci.insight.171962
|
| PII |
171962
|
| PMID |
37991021
|
| PMC |
PMC10721323
|
| MeSH |
Animals
Female
Humans
Mice
NF-kappa B* / metabolism
Nuclear Proteins
Osteoclasts / metabolism
Osteoporosis* / drug therapy
Osteoporosis* / etiology
Osteoporosis* / prevention & control
Ovariectomy / adverse effects
Peptides / pharmacology
Peptides / therapeutic use
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126)
Saos-2(RCB0428) |
