title: A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro.
abstract: Both human and murine osteoclasts can be derived in vitro from hematopoietic cells or monocytes that are co-cultured with osteoblasts or marrow-derived stromal cells. The osteoclastogenic stimulus provided by murine osteoblasts and marrow-derived stromal cells is now known to be mediated by osteoclast differentiation factor (ODF), a membrane-bound tumor necrosis factor-related ligand. This study demonstrates that mouse spleen cells and monocytes form osteoclasts when cultured in the presence of macrophage-colony stimulating factor (M-CSF) and a soluble form of murine ODF (sODF). Numerous multinucleated osteoclasts expressing tartrate resistant acid phosphatase (TRAP) and calcitonin receptor (CTR) formed within 7 days of culture and engaged in extensive lacunar bone resorption. Osteoclast number and bone resorption area was dependent on sODF concentration. Long-term cultured human monocytes also formed bone resorbing osteoclasts in response to co-stimulation by sODF and M-CSF, although this required more than 11 days in culture. This human osteoclast differentiation was strongly inhibited by granulocyte-macrophage colony stimulating factor. This study further characterises murine osteoclast differentiation caused by sODF and M-CSF co-stimulation in vitro, and shows that the same co-stimulation causes human osteoclast differentiation to occur. We propose that this methodology can be employed to investigate the direct effects of cytokines and other factors on human osteoclast differentiation.
authors.affiliation: The University of Melbourne, Department of Medicine and St Vincent's Institute of Medical Research, Fitzroy, Australia. j.quinn@medicine.unimelb.edu.au
authors.forename: J M
authors.initials: JM
authors.lastname: Quinn
authors.forename: J
authors.initials: J
authors.lastname: Elliott
authors.forename: M T
authors.initials: MT
authors.lastname: Gillespie
authors.forename: T J
authors.initials: TJ
authors.lastname: Martin
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D002478:Cells, Cultured; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin / Q000032:analysis
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018003:Receptors, Calcitonin; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase