Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK Signalling. (September 2015)

• Record Type: Journal Article
• Authors: Thummuri, Dinesh; Jeengar, Manish Kumar; Shrivastava, Shweta; Nemani, Harishankar; Ramavat, Ravindar Naik; Chaudhari, Pradip; Naidu, V.G.M.
• Is Part Of: Pharmacological research. Volume 99(2015:Sep.)
• Page Start: 63
• Page End: 73
• Publication Date: 2015-09
• Subjects: TQ thymoquinone -- RANKL receptor activator of nuclear factor kappa B ligand, receptor activated nuclear factor kappa B (NF-KB) -- TRAF6 TNF receptor-associated factor 6 -- LPS lipopolysaccharide -- DC-STAMP dendritic cell-specific transmembrane protein -- BMC bone mineral content -- BMD bone mineral density -- Tb.th. trabecular thickness -- Tb.sp. trabecular space -- TRAP tartrate-resistant acid phosphatase; Thymoquinone -- Osteoclastogenesis -- Osteolysis -- RANKL -- NF-KB; Thymoquinone (PubChem CID: 10281) -- Lipopolysaccharide (PubChem CID: 11970143) -- Tamoxifen (PubChem CID: 2733526) -- Dimethyl sulfoxide (PubChem CID: 2733526) -- Thiazolyl blue tetrazolium bromide (PubChem CID: 64965) -- Hydrogen peroxide (PubChem CID: 784) -- DC-FDA (PubChem CID: 104913) -- Ketamine (PubChem CID: 3821) -- Xylazine (PubChem CID: 5707); Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2015.05.006
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Osteoclasts are multinuclear giant cells responsible for bone resorption in inflammatory bone diseases such as osteoporosis, rheumatoid arthritis and periodontitis. Because of deleterious side effects with currently available drugs the search continues for novel effective and safe therapies. Thymoquinone (TQ), the major bioactive component of Nigella sativa has been investigated for its anti-inflammatory, antioxidant and anticancer activities. However, its effects in osteoclastogenesis have not been reported. In the present study we show for the first time that TQ inhibits nuclear factor-KB ligand (RANKL) induced osteoclastogenesis in RAW 264.7 and primary bone marrow derived macrophages (BMMs) cells. RANKL induced osteoclastogenesis is associated with increased expression of multiple transcription factors via activation of NF-KB, MAPKs signalling and reactive oxygen species (ROS). Mechanistically TQ blocked the RANKL induced NF-KB activation by attenuating the phosphorylation of IkB kinase (IKKα/β). Interestingly, in RAW 264.7 cells TQ inhibited the RANKL induced phosphorylation of MAPKs and mRNA expression of osteoclastic specific genes such as TRAP, DC-STAMP, NFATc1 and c-Fos. In addition, TQ also decreased the RANKL stimulated ROS generation in macropahges (RAW 264.7) and H2 O2 induced ROS generation in osteoblasts (MC-3T3-E1). Consistent with in vitro results, TQ inhibited lipopolysaccharide (LPS) induced bone resorption by suppressing the osteoclastogenesis. Indeed, micro-CT analysis showed that bone mineral density (BMD) and bone architecture parameters were positively modulated by TQ. Taken together our data demonstrate that TQ has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-KB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.