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MR Vol.14 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.14 No.1 |
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Osteoclastic bone resorption through receptor
tyrosine kinase and extracellular signal-regulated kinase signaling
in mature osteoclasts |
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| Hiroshi Kawaguchi1 , Mika Katagiri2 and Daichi
Chikazu2 |
(1) Department of Orthopaedic Surgery, Faculty
of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo,
113-8655, Japan
(2) Department of Oral and Maxillofacial Surgery, University of Tokyo, Tokyo,
Japan |
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| Abstract |
| Abstract It has recently been suggested that
signaling through receptor tyrosine kinases (RTKs) expressed on mature
osteoclasts is involved in osteoclastic bone resorption. This study
investigated the role and mechanism of two major RTKs expressed on
mature osteoclasts, fibroblast growth factor receptor type 1 (FGFR1)
and Tyro 3. Among the FGF receptors (FGFR1?4), only FGFR1 was detected
on isolated mouse osteoclasts, while all FGFRs were identified on
mouse osteoblasts. Tyro 3 was seen only in mature osteoclasts among
bone cells. FGF-2 moderately stimulated pit formation by isolated
rabbit osteoclasts at low concentrations (10?12M), whereas at high
concentrations (10?9M) it strongly stimulated pit formation by unfractionated
bone cells. Gas6, the ligand of Tyro 3, was expressed ubiquitously
in bone cells and stimulated osteoclast function to form resorbed
pits on a dentine slice. Both FGF-2 and Gas6 upregulated the phosphorylation
of cellular proteins, including extracellular signal-regulated kinase
(ERK), and increased the kinase activity of immunoprecipitated FGFR1
and Tyro 3, respectively, in mouse osteoclasts. The stimulation of
these cytokines on mouse and rabbit osteoclast functions was abrogated
by PD98059, a specific inhibitor of ERK. These results strongly suggest
that these cytokines act directly on mature osteoclasts through the
activation of RTKs and ERK, causing the stimulation of bone resorption. |
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| Key words |
| Key words Bone resorption - Fibroblast growth
factor - Gas6 - Osteoclast - Tyro 3 |
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