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
Human and Animal Cells MC3T3-E1(RCB1126) Saos-2(RCB0428)