title: Expression of the cell-adhesion molecule VCAM-1 by stromal cells is necessary for osteoclastogenesis.
abstract: Osteoblastic cells have been shown to be involved in osteoclast formation through cell to cell contacts. This study was designed to examine the possible function of vascular cell adhesion molecule 1 (VCAM-1) during osteoclastogenesis. As a source for stromal cells we used the recently established mouse bone marrow stromal cell line mBMS-B1 which has the ability to support osteoclastogenesis when used in co-culture with a crude spleen cell suspension. mBMS-B1 cells express a single approximately 3.9 kb VCAM-1 mRNA species. Expression was low under basal culture conditions and a 5-10-fold increase was observed in the presence of 1,25(OH)2D3. Cell surface expression of VCAM-1 examined by FACS analysis was increased about 2-fold after 1,25(OH)2D3 treatment. Immunoprecipitation of cell surface expressed VCAM-1 or total VCAM-1 protein using the anti-VCAM-1 monoclonal antibody MK2.7 resulted in a single approximately 110 kDa protein on SDS-PAGE. Induction by 1,25(OH)2D3 was about 2-5-fold on day 3. The stromal cell-osteoclast precursor cell interaction was investigated in a co-culture of the mBMS-B1 and mouse spleen cells in the presence of 1,25(OH)2D3. The monoclonal antibody MK2.7 which is known to block hemopoietic-stromal cell recognition inhibited the formation of osteoclasts when added to the co-culture at day 2 but not day 4. These data suggest that VCAM-1 is involved in the interaction between stromal cells and osteoclastic precursor cells during osteoclastogenesis presumably most important during early stages of the formation of osteoclasts.
authors.affiliation: Department of Arthritis and Bone Metabolism, Novartis Pharma, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Feuerbach
authors.forename: J H
authors.initials: JH
authors.lastname: Feyen
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002450:Cell Communication; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D002117:Calcitriol