SNX10 Plays a Critical Role in MMP9 Secretion via JNK-p38-ERK Signaling Pathway

Journal of Cellular Biochemistry
Chun ZhouXiaoyan Shen

Abstract

Matrix metalloproteinases (MMPs) plays a critical role in the degradation of extracellular matrix (ECM). Sorting nexin (SNX) 10 is a member of the SNX family, which functions in regulation of endosomal sorting and osteoclast activation, has been implicated to play an important role in the bone erosion of rheumatoid arthritis. In this study, we aimed to investigate the possible role of SNX10 on MMP9 secretion and the potential mechanism. By immunostaining and co-immunoprecipitation, we found that SNX10 was extensively co-localized with MMP9, indicating that SNX10 might participate in MMP9 trafficking. After knocking down SNX10 via siRNA, the secretion and activity of MMP9 was significantly reduced, but the amount of protein was increased. By contraries, over-expression of SNX10 could increase the secretion and activity levels. Deficiency of SNX10 impaired the differentiation and bone resorption function of osteoclast, with a low activity of MMP9 compared to WT one. In SNX10 knockout osteoclast, the phosphorylation levels of JNK, p38, and ERK were obviously down-regulated. Our results first identified the role of SNX10 in MMP9 trafficking and secretion, and provided an evidence for SNX10 as a possible therapeutic target for bone ...Continue Reading

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Citations

Jan 18, 2018·Current Osteoporosis Reports·Eleonora PalaganoAnna Villa
Mar 7, 2019·Biochemical Society Transactions·Pei Ying NgNathan John Pavlos
Jan 26, 2021·International Journal of Nanomedicine·Wei-Lian BaoWeixing Shen
May 12, 2021·Journal of Cell Science·Maayan Barnea-ZoharAri Elson
Oct 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Bhavyashree SureshYamuna Krishnan

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