LAMP-2 Is Involved in Surface Expression of RANKL of Osteoblasts In Vitro

International Journal of Molecular Sciences

Paul Saftig¹  Wikky Tigchelaar-Gutter²  Vincent Everts³  JolandaM. A. Hogervorst³  TeunJ. de Vries⁴  InekeD.C. Jansen⁴ 

[1] Biochemisches Institut, Christian-Albrechts-Universität, 24098 Kiel, Germany;Center for Microscopic Research, Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Amsterdam, 1081 LA Amsterdam, The Netherlands;Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081 LA Amsterdam, The Netherlands;

关键词: LAMP-2;    RANKL;    osteoblasts;    osteoclasts;   

DOI  :  10.3390/ijms21176110

来源: DOAJ

【 摘 要 】

Lysosome associated membrane proteins (LAMPs) are involved in several processes, among which is fusion of lysosomes with phagosomes. For the formation of multinucleated osteoclasts, the interaction between receptor activator of nuclear kappa β (RANK) and its ligand RANKL is essential. Osteoclast precursors express RANK on their membrane and RANKL is expressed by cells of the osteoblast lineage. Recently it has been suggested that the transport of RANKL to the plasma membrane is mediated by lysosomal organelles. We wondered whether LAMP-2 might play a role in transportation of RANKL to the plasma membrane of osteoblasts. To elucidate the possible function of LAMP-2 herein and in the formation of osteoclasts, we analyzed these processes in vivo and in vitro using LAMP-2-deficient mice. We found that, in the presence of macrophage colony stimulating factor (M-CSF) and RANKL, active osteoclasts were formed using bone marrow cells from calvaria and long bone mouse bone marrow. Surprisingly, an almost complete absence of osteoclast formation was found when osteoclast precursors were co-cultured with LAMP-2 deficient osteoblasts. Fluorescence-activated cell sorting FACS analysis revealed that plasma membrane-bound RANKL was strongly decreased on LAMP-2 deficient osteoblasts. These results suggest that osteoblastic LAMP-2 is required for osteoblast-induced osteoclast formation in vitro.

【 授权许可】

Unknown