title: The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice.
abstract: Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Vinik
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Shatz-Azoulay
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alessia
authors.initials: A
authors.lastname: Vivanti
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Navit
authors.initials: N
authors.lastname: Hever
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Karmona
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Vlad
authors.initials: V
authors.lastname: Brumfeld
authors.affiliation: Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Saja
authors.initials: S
authors.lastname: Baraghithy
authors.affiliation: Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Malka
authors.initials: M
authors.lastname: Attar-Lamdar
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Sigalit
authors.initials: S
authors.lastname: Boura-Halfon
authors.affiliation: Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Bab
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yehiel
authors.initials: Y
authors.lastname: Zick
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D037161:Galectins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D061251:Primary Cell Culture; D011485:Protein Binding; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D037161:Galectins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D008562:Membrane Glycoproteins; C474081:Mrc2 protein, mouse; D053245:RANK Ligand; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D055293:Receptors, Urokinase Plasminogen Activator; C505689:Tnfsf11 protein, mouse; D025521:Tumor Suppressor Proteins; C526554:galectin-8, mouse
keywords: animal lectins; bone mass; cell biology; human; human biology; medicine; mouse; osteoclastogenesis