title: Regulation of RANKL-induced osteoclastic differentiation by vascular cells.
abstract: Vascular calcification is a regulated process of biomineralization resembling osteogenesis. Many bone-related factors, including resorptive osteoclast-like cells, although in low abundance, have been found in calcified atherosclerotic lesions. The regulatory mechanisms governing them in the vasculature, however, are not clear. Previously, we found that calcifying vascular cells (CVC), a subpopulation of bovine aortic smooth muscle cells (BASMC), undergo osteoblastic differentiation and form mineralized nodules. Since osteoblasts and marrow stromal preosteoblasts regulate osteoclastic differentiation in bone, we hypothesized that vascular cells also regulate differentiation of osteoclastic precursors in the artery wall. Peripheral blood monocytes, which are osteoclast precursors, were co-cultured with CVC or BASMC. Results showed that monocytes co-cultured with both of the vascular cells yielded fewer resorption pits than monocytes cultured alone. Furthermore, monocytes co-cultured with CVC had fewer resorption pits than those co-cultured with BASMC. Conditioned media from the vascular cells also inhibited resorptive activity of monocytes suggesting that the inhibitory effect was mediated in part by soluble factors. Compared with BASMC, CVC had lower mRNA expression for osteopontin, which promotes osteoclast attachment, but greater mRNA expression for the soluble inhibitory cytokine, IL-18. Increased osteoclastic differentiation was observed when neutralizing antibody to IL-18 receptor was added to the cultures of preosteoclasts with CVC conditioned media. Osteoprotegerin, another osteoclast inhibitory cytokine, was expressed at similar levels in both cultures. These results suggest that vascular cells inhibit osteoclastic differentiation, and that CVC have greater inhibitory effects than BASMC.
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, 10833 LeConte Avenue, Los Angeles, CA 90095-1679, USA. ytintut@mednet.ucla.edu
authors.forename: Yin
authors.initials: Y
authors.lastname: Tintut
authors.forename: Moeen
authors.initials: M
authors.lastname: Abedin
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.forename: Andrea
authors.initials: A
authors.lastname: Choe
authors.forename: Jina
authors.initials: J
authors.lastname: Lim
authors.forename: Linda L
authors.initials: LL
authors.lastname: Demer
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D001862:Bone Resorption; D002352:Carrier Proteins / Q000494:pharmacology*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053495:Osteopontin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D053495:Osteopontin