1. Osteoblastic heparan sulfate glycosaminoglycans control bone remodeling by regulating Wnt signaling and the crosstalk between bone surface and marrow cells
- Author
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Agnès Ostertag, Carole Le Henaff, Monique Frain, Caroline Marty, Claudine Blin-Wakkach, Dominique Modrowski, Pierre J. Marie, Eric Haÿ, Martine Cohen-Solal, Yohann Jouan, Rafik Mansouri, Valérie Geoffroy, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), BioEmergences, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Cancer Research ,MESH: Bone Resorption ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Apoptosis ,Bone remodeling ,Glycosaminoglycan ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Osteogenesis ,MESH: Gene Expression Regulation, Developmental ,MESH: Animals ,MESH: Osteogenesis ,Wnt Signaling Pathway ,Glycosaminoglycans ,Regulation of gene expression ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Chemistry ,MESH: Bone Marrow Cells ,MESH: Wnt Signaling Pathway ,Wnt signaling pathway ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Gene Expression Regulation, Developmental ,MESH: Glycosaminoglycans ,Cell Differentiation ,Heparan sulfate ,MESH: RANK Ligand ,Cell biology ,Crosstalk (biology) ,030220 oncology & carcinogenesis ,Original Article ,Bone Remodeling ,MESH: Cell Differentiation ,medicine.medical_specialty ,MESH: Mice, Transgenic ,Transgene ,Immunology ,Bone Marrow Cells ,Mice, Transgenic ,MESH: Syndecan-2 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,MESH: Heparitin Sulfate ,MESH: Bone Remodeling ,Internal medicine ,medicine ,Animals ,Humans ,Bone Resorption ,MESH: Mice ,MESH: Osteoblasts ,MESH: Humans ,Osteoblasts ,MESH: Apoptosis ,RANK Ligand ,Correction ,Mesenchymal Stem Cells ,Cell Biology ,030104 developmental biology ,Endocrinology ,MESH: Mesenchymal Stromal Cells ,Heparitin Sulfate ,Syndecan-2 - Abstract
Stimulating bone formation is an important challenge for bone anabolism in osteoporotic patients or to repair bone defects. The osteogenic properties of matrix glycosaminoglycans (GAGs) have been explored; however, the functions of GAGs at the surface of bone-forming cells are less documented. Syndecan-2 is a membrane heparan sulfate proteoglycan that is associated with osteoblastic differentiation. We used a transgenic mouse model with high syndecan-2 expression in osteoblasts to enrich the bone surface with cellular GAGs. Bone mass was increased in these transgenic mice. Syndecan-2 overexpression reduced the expression of receptor activator of NF-kB ligand (RANKL) in bone marrow cells and strongly inhibited bone resorption. Osteoblast activity was not modified in the transgenic mice, but bone formation was decreased in 4-month-old transgenic mice because of reduced osteoblast number. Increased proteoglycan expression at the bone surface resulted in decreased osteoblastic and osteoclastic precursors in bone marrow. Indeed, syndecan-2 overexpression increased apoptosis of mesenchymal precursors within the bone marrow. However, syndecan-2 specifically promoted the vasculature characterized by high expression of CD31 and Endomucin in 6-week-old transgenic mice, but this was reduced in 12-week-old transgenic mice. Finally, syndecan-2 functions as an inhibitor of Wnt-β-catenin–T-cell factor signaling pathway, activating glycogen synthase kinase 3 and then decreasing the Wnt-dependent production of Wnt ligands and R-spondin. In conclusion, our results show that GAG supply may improve osteogenesis, but also interfere with the crosstalk between the bone surface and marrow cells, altering the supporting function of osteoblasts.
- Published
- 2016