RRC ID 72359
Author Fan X, Fan D, Gewant H, Royce CL, Nanes MS, Rubin J.
Title Increasing membrane-bound MCSF does not enhance OPGL-driven osteoclastogenesis from marrow cells.
Journal Am J Physiol Endocrinol Metab
Abstract Macrophage colony-stimulating factor (MCSF) and osteoprotegerin ligand (OPGL), both produced by osteoblasts/stromal cells, are essential factors for osteoclastogenesis. Whether local MCSF levels regulate the amount of osteoclast formation is unclear. Two culture systems, ST-2 and Chinese hamster ovary-membrane-bound MCSF (CHO-mMCSF)-Tet-OFF cells, were used to study the role of mMCSF in osteoclast formation. Cells from bone marrow (BMM) or spleen were cultured with soluble OPGL on glutaraldehyde-fixed cell layers; osteoclasts formed after 7 days. Osteoclast number was proportional to the amount of soluble OPGL added. In contrast, varying mMCSF levels in the ST-2 or CHO-mMCSF-Tet-OFF cell layers, respectively by variable plating or by addition of doxycycline, did not affect BMM osteoclastogenesis: 20-450 U of mMCSF per well generated similar osteoclast numbers. In contrast, spleen cells were resistant to mMCSF: osteoclastogenesis required > or = 250 U per well and further increased as mMCSF rose higher. Our results demonstrate that osteoclast formation in the local bone environment is dominated by OPGL. Increasing mMCSF above basal levels does not further enhance osteoclast formation from BMMs, indicating that mMCSF does not play a dominant regulatory role in the bone marrow.
Volume 280(1)
Pages E103-11
Published 2001-1-1
DOI 10.1152/ajpendo.2001.280.1.E103
PMID 11120664
MeSH Animals Bone Marrow Cells / cytology* Bone Marrow Cells / physiology* CHO Cells Calcitriol / pharmacology Calcium Channel Agonists / pharmacology Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Differentiation / drug effects Cell Differentiation / physiology Cell Division / immunology Cricetinae Dexamethasone / pharmacology Gene Expression / physiology Glucocorticoids / pharmacology Macrophage Colony-Stimulating Factor / genetics Macrophage Colony-Stimulating Factor / metabolism* Macrophages / cytology Male Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Membrane Proteins / metabolism Mice Mice, Inbred C57BL Osteoclasts / cytology* Osteoclasts / physiology* RANK Ligand Receptor Activator of Nuclear Factor-kappa B Spleen / cytology Stem Cells / cytology Stem Cells / physiology Stromal Cells / cytology Stromal Cells / physiology Tetracyclines
IF 3.469
Human and Animal Cells ST2(RCB224)