Alternate signaling pathways selectively regulate binding of insulin-like growth factor I and II on fetal rat bone cells

✍ Scribed by Thomas L. Mccarthy; Changhua Ji; Sandra Casinghino; Michael Centrella

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 170 KB
• Volume: 68
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19980315)68:4<446::aid-jcb5>3.0.co;2-q

✦ Synopsis

Bone cells synthesize and respond to IGF-I and IGF-II which contribute to bone remodeling and linear growth. In osteoblasts, prostaglandin (PG)E 2 stimulates IGF-I but not IGF-II synthesis through a cAMP-dependent protein kinase A (PKA)-related event. However, protein kinase C (PKC) activation by PGE 2 enhances replication and protein synthesis by less differentiated periosteal cells more so than in osteoblast-enriched cultures from fetal rat bone. Using various PGs and other PKA and PKC pathway activators, the importance of these aspects of PGE 2 activity has now been examined on IGF receptors in these bone cell culture models. PGE 2 and other agents that activate PKA enhanced 125 I-IGF-II binding to type 2 IGF receptors on both cell populations. In contrast, agents that activate PKC enhanced 125 I-IGF-I binding to type 1 receptors on less differentiated bone cells, and of these, only phorbol myristate acetate (PMA), which activates PKC in a receptor-independent way, was effective in osteoblast-enriched cultures. No stimulator increased total type 1 receptor protein in either cell population. Consequently, ligand binding to type 1 and type 2 IGF receptors is differentially modulated by specific intracellular pathways in bone cells. Importantly, changes in apparent type 1 receptor number occur rapidly and may do so at least in part through post-translational effects. These results may help to predict new ways to manipulate autocrine or paracrine actions by IGFs in skeletal tissue.