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Osteoprotegerin and osteoprotegerin ligand effects on osteoclast formation from human peripheral blood mononuclear cell precursors
Author(s) -
Shalhoub Victoria,
Faust Judy,
Boyle William J.,
Dunstan Colin R.,
Kelley Mike,
Kaufman Steve,
Scully Sheila,
Van Gwyneth,
Lacey David L.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990201)72:2<251::aid-jcb9>3.0.co;2-w
Subject(s) - osteoclast , osteoprotegerin , bone resorption , peripheral blood mononuclear cell , endocrinology , medicine , chemistry , rankl , resorption , acid phosphatase , tartrate resistant acid phosphatase , stromal cell , biology , receptor , in vitro , biochemistry , activator (genetics) , enzyme
Osteoprotegerin (OPG) and its ligand (OPGL) negatively and positively regulate osteoclastogenesis in the mouse. OPG inhibits osteoclastogenesis by sequestering its ligand, OPGL, the osteoclast differentiation and activation factor. This study demonstrates the effects of soluble muOPGL and huOPG on the developing human osteoclast phenotype, on bone slices, using peripheral blood mononuclear cells (PBMCs), cultured for 2 weeks, without stromal cells. OPGL (2–50 ng/ml), in combination with CSF‐1, hydrocortisone (HC), and 1,25(OH) 2 D 3 , increases the size of osteoclast‐like cells on bone, as defined by the acquisition of osteoclast markers: vitronectin receptor (VR), tartrate‐resistant acid phosphatase (TRAP), multinuclearity, and bone resorption. By 14 days, with 20 ng/ml OPGL, the largest cells/10× field have achieved an average diameter of 163 ± 38 μm, but only ∼10–20 μm in its absence and the number of osteoclast‐like cells/mm 2 bone surface is about 128. By scanning electron microscopy, OPGL‐treated (20‐ng/ml) cultures contain small osteoclast‐like cells on bone with ruffled “apical” surfaces by day 7; by day 15, large osteoclast‐like cells are spread over resorption lacunae. At 15 ng/ml OPGL, about 37% of the bone slice area is covered by resorption lacunae. OPG (5–250 ng/ml) antagonizes the effects of OPGL on the morphology of the osteoclast‐like cells that form, as well as bone erosion. For cells grown on plastic, Cathepsin K mRNA levels, which are barely detectable at plating, are elevated 7‐fold, by 5 days, in the presence, not the absence, of OPGL (20 ng/ml) + CSF‐1 (25 ng/ml). Similar findings are observed in experiments performed in the absence of HC and 1,25(OH) 2 D 3 , indicating that HC and 1,25(OH) 2 D 3 are not needed for OPGL‐induced osteoclast differentiation. In conclusion, this study confirms a pivotal role for OPGL and OPG in the modulation of human osteoclast differentiation and function, suggesting a use for OPG for treating osteoclast‐mediated bone disease in humans. J. Cell. Biochem. 72:251–261, 1999. © 1999 Wiley‐Liss, Inc.