Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 119, Issue 4, Pages 813-825Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI36809
Keywords
-
Categories
Funding
- Korean government (MEST) [R0A-2008-000-20001-0]
- KOSEF [F104AC010002-07A0301, M1-0641-35-0002, R13-2005-005-01004-0]
- National Core Research Facility (NCRC) program [R15-2006-020]
- NIH [AR053843, DE019381]
- Brain Korea 21 Project
- National Research Foundation of Korea [R13-2005-005-01004-0, R0A-2008-000-20001-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Regulation of the formation and function of bone-resorbing osteoclasts (OCs) is a key to understanding the pathogenesis of skeletal disorders. Gene-targeting studies have shown that the RANK signaling pathway plays a critical role in OC differentiation and function. Although pharmaceutical blockade of RANK may be a viable strategy for preventing bone destruction, RANK is implicated in multiple biological processes. Recently, a cytoplasmic: motif of RANK was identified that may be specifically involved in OC differentiation. Here, we developed a cell-permeable inhibitor termed the RANK receptor inhibitor (RRI), which targets this motif. The RRI peptide blocked RANKL-induced OC formation from murine bone marrow-derived macrophages. Furthermore, RRI inhibited the resorptive function of OCs and induced OC apoptosis. Treatment with the peptide impaired downstream signaling of RANK linked to Vav3, Rac1, and Cdc42 and resulted in disruptions of the actin cytoskeleton in differentiated OCs. in addition, RRI blocked inflammation-induced bone destruction and protected against ovariectomy-induced bone loss in mice. These data may be useful in the development of selective therapeutic agents for the treatment of osteoporosis and other bone diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available