Momordin I, an inhibitor of AP-1, suppressed osteoclastogenesis through inhibition of NF-κB and AP-1 and also reduced osteoclast activity and survival

• Published in: Biochemical and biophysical research communications Vol. 337; no. 3; pp. 815 - 823
• Main Authors: Hwang, Yun Ha, Lee, Jung Wook, Hahm, Eun-Ryeong, Jung, Kyung Chae, Lee, Ju Hyung, Park, Chi Hoon, Rhee, Ho Sung, Ryu, Je Man, Kim, Hyun-Kyung, Yang, Chul-Hak
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 25.11.2005
• Subjects: AP-1; Bone resorption; Momordin I; NF-κB; Osteoclast; Osteoclastogenesis; RANKL; Survival; Osteoclastogenesis; Bone resorption; NF-κB; RANKL; Momordin I; Osteoclast; AP-1; Survival
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.09.113

Osteoclasts originating from hematopoietic precursor cells differentiate into multinucleated cells through multiple steps. The essential roles of NF-κB and AP-1 in osteoclast differentiation have been clearly demonstrated in numerous studies. c-Fos, a component of AP-1 transcription factor, plays a key role in osteoclast differentiation. Recently, we found a strong inhibitor of AP-1 transcriptional activity, named momordin I, based on the structure of oleanolic acid glycosides and originally isolated from Ampelopsis radix. So, we hypothesized that momordin I might be able to regulate osteoclast formation, activity, and survival. Here, we report the ability of momordin I to suppress osteoclastogenesis in a co-cultured system and a RANKL-induced osteoclast precursor system. Momordin I remarkably inhibited the activation of NF-κB as well as AP-1 in RANKL-induced RAW264.7 cells, in which momordin I appeared to target IκB degradation and c-Fos expression, respectively, but not MAPK signaling pathways. The ability of momordin I to change the ratio of RANKL and OPG in primary osteoblasts was partially responsible for the reduction of osteoclast formation. Furthermore, pit formation on dentin slices was suppressed by momordin I with stimulating actin ring disruption. Our results also showed that momordin I highly shortened osteoclast lifespan and induced osteoclast apoptosis. In conclusion, the present results demonstrate for the first time that momordin I is a potent inhibitor of osteoclast differentiation via the reduction of NF-κB and AP-1, and also suppresses osteoclast function and survival.