Premium
Insulin‐like growth factor‐I mediates osteoclast‐like cell formation stimulated by parathyroid hormone
Author(s) -
Kaji Hiroshi,
Sugimoto Toshitsugu,
Kanatani Masanori,
Nishiyama Katsuhito,
Nasu Masamichi,
Chihara Kazuo
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199707)172:1<55::aid-jcp6>3.0.co;2-c
Subject(s) - osteoclast , parathyroid hormone , medicine , endocrinology , growth factor , insulin like growth factor , growth hormone , hormone , insulin , chemistry , somatomedin , microbiology and biotechnology , cancer research , biology , receptor , calcium
There have been several lines of evidence that parathyroid hormone (PTH) stimulates production of insulinlike growth factor I (IGF‐I) in bone and that IGF‐I stimulates osteoclast formation. Thus, the present study was performed to clarify the possible role of IGF‐I in PTH‐stimulated osteoclastlike cell formation and the role of PTH‐responsive dual signal transduction systems (cyclic [c] AMP‐dependent protein kinase [PKA] and calcium/protein kinase C [PKC]) in its mechanism. Treatment with anti‐IGF‐I antibody (1–10 μg/ml) partially but significantly blocked hPTH‐(1‐34)‐stimulated osteoclastlike cell formation in unfractionated mouse bone cell cultures, although it did not affect osteoclastlike cell formation stimulated by 1,25‐dihydroxyvitamin D 3 . Rp‐cAMPS (10 ‐4 M), a direct PKA inhibitor, as well as two types of PKC inhibitors, H‐7 (10 μM) and staurosporine (3 nM), and dantrolene (10 ‐5 M), an inhibitor of calcium mobilization from intracellular calcium stores, all significantly blocked PTH‐stimulated osteoclastlike cell formation. Anti‐IGF‐I antibody (3 μg/ml) significantly blocked osteoclastlike cell formation stimulated by 10 ‐4 M dbcAMP, 10 ‐4 M Sp‐cAMPS, a direct PKA activator, and 10 ‐5 M forskolin in mouse bone cell cultures. Dibutyryl cAMP, forskolin, and hPTH‐(1‐34) significantly stimulated mRNA expression of both IGF‐I and IGF‐binding protein 5 (IGFBP‐5) in these cultures, but neither 10 ‐7 M PMA, a PKC activator, nor 10 ‐7 M A23187 did. Moreover, anti‐IGF‐I antibody significantly blocked osteoclastlike cell formation stimulated by the conditioned medium from MC3T3‐E1 cells pretreated with 10 ‐8 PTH‐(1‐34), which induced IGF‐I and IGFBP‐5 mRNA expression in these cells. In conclusion, the present study indicates that IGF‐I mediates osteoclastlike cell formation stimulated by PTH and that the PKA pathway is involved in its mechanism. However, IGF‐I does not seem to be the sole effector molecule to be active in this system. J. Cell. Physiol. 172:55–62, 1997. © 1997 Wiley‐Liss, Inc.