Fas/S1P 1 crosstalk via NF-κB activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis

• Published in: Biochemical and biophysical research communications 2017-09, Vol.490 (4), p.1274-1281
• Main Authors: Hutami, Islamy Rahma, Izawa, Takashi, Mino-Oka, Akiko, Shinohara, Takehiro, Mori, Hiroki, Iwasa, Akihiko, Tanaka, Eiji
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Autoimmunity; Bone Marrow Cells - drug effects; Bone Marrow Cells - immunology; Bone Marrow Cells - pathology; Bone Resorption - genetics; Bone Resorption - immunology; Bone Resorption - pathology; Bone Resorption - prevention & control; Cell Differentiation; Disease Models, Animal; fas Receptor - genetics; fas Receptor - immunology; Female; Gene Expression Regulation; Lysophospholipids - immunology; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; Mice; Mice, Inbred MRL lpr; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - immunology; Neuropeptides - genetics; Neuropeptides - immunology; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - immunology; Osteoclasts - drug effects; Osteoclasts - immunology; Osteoclasts - pathology; Osteogenesis - drug effects; Osteogenesis - immunology; Peptides - pharmacology; Phosphotransferases (Alcohol Group Acceptor) - genetics; Phosphotransferases (Alcohol Group Acceptor) - immunology; Primary Cell Culture; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - immunology; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - immunology; RANK Ligand - genetics; RANK Ligand - immunology; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - immunology; Signal Transduction; Sphingosine - analogs & derivatives; Sphingosine - immunology; Temporomandibular Joint - drug effects; Temporomandibular Joint - immunology; Temporomandibular Joint - pathology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.07.006

Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice. Initially, greater osteoclast production was observed in vitro from bone marrow macrophages obtained from MRL/lpr mice due to enhanced phosphorylation of NF-κB, as well as Akt and MAPK, to receptor activator of nuclear factor-κB ligand (RANKL). Expression of sphingosine 1-phosphate receptor 1 (S1P ) was also significantly upregulated in the condylar cartilage. S1P was found to be required for S1P-induced migration of osteoclast precursor cells and downstream signaling via Rac1. When SN50, a synthetic NF-κB-inhibitory peptide, was applied to the MRL/lpr mice, subchondral trabecular bone loss was reduced and both production of osteoclastogenesis markers and sphingosine kinase (Sphk) 1/S1P signaling were reduced. Thus, the present results suggest that Fas/S1P signaling via activation of NF-κB in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ.