In:
Journal of Bone and Mineral Research, Wiley, Vol. 13, No. 1 ( 1998-01), p. 50-58
Abstract:
The colony stimulating factor 1 (CSF‐1) regulates osteoclastogenesis and bone resorption. Mutations in the CSF‐1 gene cause an osteopetrosis characterized by the absence of osteoclasts. Mature osteoclasts respond to CSF‐1 with inhibition of bone resorption and an increment of cell spreading. Herein we demonstrate that CSF‐1–induced osteoclast spreading depends on the substrate the osteoclast interacts with and requires integrity of the vitronectin receptor and of the c‐ src proto‐oncogene. Rabbit osteoclasts were allowed to attach to glass, serum, osteopontin, and bone substrates, and were treated with 10 ng/ml human recombinant CSF‐1 for 4 h. In osteoclasts plated on glass, the cytokine induced 70% inhibition of bone resorption and 1.8‐fold stimulation of cell spreading, without changes in podosome expression and microfilament array. In contrast, CSF‐1 induced a 2.5‐fold increase of osteoclasts showing filopodia, and a 9.5‐fold increase of osteoclasts presenting lamellipodia, indicating that membrane motility was required for cell spreading. Osteoclasts plated on serum substrates showed a 50% reduction of spontaneous spreading. However, in this circumstance, CSF‐1 still stimulated an increase of osteoclast area. In osteoclasts cultured on osteopontin substrate or on bone slices, an inhibition of CSF‐1–induced osteoclast spreading was observed. To establish involvement of the vitronectin receptor and c‐ src proto‐oncogene, cells were treated with the α v β 3 integrin neutralizing antibody, LM609, or c‐ src antisense oligonucleotides, which reduced CSF‐1–induced osteoclast spreading by 57% and 60%, respectively. The results demonstrate that CSF‐1–induced osteoclast spreading requires both the vitronectin receptor and the c‐ src proto‐oncogene and that this action is modulated by the adhesion substrata.
Type of Medium:
Online Resource
ISSN:
0884-0431
,
1523-4681
DOI:
10.1359/jbmr.1998.13.1.50
Language:
English
Publisher:
Wiley
Publication Date:
1998
detail.hit.zdb_id:
2008867-X
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