| First Author | Hutami IR | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 490 |
| Issue | 4 | Pages | 1274-1281 |
| PubMed ID | 28687489 | Mgi Jnum | J:312023 |
| Mgi Id | MGI:6710846 | Doi | 10.1016/j.bbrc.2017.07.006 |
| Citation | Hutami IR, et al. (2017) Fas/S1P1 crosstalk via NF-kappaB activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis. Biochem Biophys Res Commun 490(4):1274-1281 |
| abstractText | 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-kappaB, as well as Akt and MAPK, to receptor activator of nuclear factor-kappaB ligand (RANKL). Expression of sphingosine 1-phosphate receptor 1 (S1P1) was also significantly upregulated in the condylar cartilage. S1P1 was found to be required for S1P-induced migration of osteoclast precursor cells and downstream signaling via Rac1. When SN50, a synthetic NF-kappaB-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/S1P1 signaling were reduced. Thus, the present results suggest that Fas/S1P1 signaling via activation of NF-kappaB in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ. |
