Suppression of NF-kappa B Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis

• Type of Material: Article
• Authors: Masayoshi Yamaguchi, Emory University; T. Vikulina, Emory University; Jack Arbiser, Emory University; M. Neale Weitzmann, Emory University
• Language: English
• Date: 2014-01-01
• Publisher: Bentham Science Publishers
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Bentham Science Publishers.
• Final Published Version (URL): http://dx.doi.org/10.2174/1566524014666140724104842
• Title of Journal or Parent Work: Current Molecular Medicine
• ISSN: 1566-5240
• Volume: 14
• Issue: 6
• Start Page: 783
• End Page: 792
• Grant/Funding Information: M. Neale Weitzmann is supported in part by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (I01BX000105); and by NIAMS grants (AR053607, AR056090 and AR059364;) and NIA grant AG040013.; Jack L. Arbiser is supported by NIAMS grant AR47901.
• Keywords: ESTROGEN DEFICIENCY; BONE-FORMATION; NF-kappa B; gentian violet; Medicine, Research & Experimental; osteoblast; DIFFERENTIATION; NECROSIS-FACTOR-ALPHA; osteoclast; OVARIECTOMIZED MICE; Research & Experimental Medicine; MC3T3 PREOSTEOBLASTS; Bone formation; TNF; osteoporosis; Science & Technology; STIMULATES OSTEOBLASTOGENESIS; INHIBITION; Life Sciences & Biomedicine; SMAD ACTIVATION
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Cell

Abstract

Skeletal mass is regulated by the coordinated action of bone forming osteoblasts and bone resorbing osteoclasts. Accelerated rates of bone resorption relative to bone formation lead to net bone loss and the development of osteoporosis, a devastating disease that predisposes the skeleton to fractures. Bone fractures are associated with significant morbidity and in the case of hip fractures, high mortality. Gentian violet (GV), a cationic triphenylmethane dye, has long been used as an antifungal and antibacterial agent and is presently under investigation as a potential chemotherapeutic and antiangiogenic agent. However, effects on bone cells have not been previously reported and the mechanisms of action of GV, are poorly understood. In this study we show that GV suppresses receptor activator of NF-κB ligand (RANKL)-induced differentiation of RAW264.7 osteoclast precursors into mature osteoclasts, but paradoxically stimulates the differentiation of MC3T3 cells into mineralizing osteoblasts. These actions stem from the capacity of GV to suppress activation of the nuclear factor kappa B (NF-κB) signal transduction pathway that is required for osteoclastogenesis, but inhibitory to osteoblast differentiation and activity. Our data reveal that GV is an inhibitor of NF-κB activation and may hold promise for modulation of bone turnover to promote a balance between bone formation and bone resorption, favorable to gain of bone mass.