title: TGF-beta enhances osteoclast differentiation in hematopoietic cell cultures stimulated with RANKL and M-CSF.
abstract: TGF-beta has been shown to inhibit and stimulate osteoclastogenesis. The purpose of this study was to evaluate the effects of TGF-beta in hematopoietic cell cultures stimulated with RANKL and M-CSF. In cocultures of hematopoietic cells and BALC cells (a calvarial-derived cell line), TGF-beta inhibited tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation. In contrast, TGF-beta enhanced TRAP-positive multinucleated cell formation up to 10-fold in hematopoietic cell cultures containing few osteoblastic/stromal cells. Likewise, TGF-beta increased the number of calcitonin receptor (CTR)-positive multinucleated and mononucleated cells in a concentration-dependent manner. An increase in cell size and multinuclearity was also observed in the presence of TGF-beta. The stimulatory effects of TGF-beta were dependent on the presence of M-CSF and RANKL. When differentiated on bovine cortical bone slices, these cells formed resorption lacunae. These results suggest that TGF-beta has a direct stimulatory effect on osteoclastogenesis in hematopoietic cells treated with RANKL and M-CSF.
authors.affiliation: Lilly Research Labs, Lilly Corporate Center, Indianapolis, Indiana, 46285, USA. Galvin_Rachelle_J_S@Lilly.com
authors.forename: R J
authors.initials: RJ
authors.lastname: Sells Galvin
authors.forename: C L
authors.initials: CL
authors.lastname: Gatlin
authors.forename: J W
authors.initials: JW
authors.lastname: Horn
authors.forename: T R
authors.initials: TR
authors.lastname: Fuson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption; D002352:Carrier Proteins / Q000494:pharmacology*; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D048429:Cell Size; D002478:Cells, Cultured; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D053245:RANK Ligand; D016601:RNA-Binding Proteins / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin / Q000032:analysis; D012886:Skull; D013154:Spleen / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C079092:MtrB protein, Bacteria; D053245:RANK Ligand; D016601:RNA-Binding Proteins; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor