Insulinlike growth factor II and transforming growth factor beta regulate collagen expression in human osteoblastlike...

Insulinlike growth factor II (IGF-II) and transforming growth factor beta (TGF-beta) are the most abundant polypeptide growth factors found in human bone matrix and are produced by human bone cells in vitro. IGF-II and TGF-beta 1 increased total protein synthesis, collagenous protein synthesis, and the steady-state level of type I procollagen mRNA in a time-dependent manner in osteoblastlike cells isolated from human bone. Type III procollagen mRNA expression was low in untreated cultures and was not affected by IGF-II or TGF-beta. TGF-beta 1 elevated type I procollagen mRNA rapidly, with the maximal observed change at 10 h. In contrast, procollagen mRNA levels increased more slowly in response to IGF-II and reached a lower maximal level than with TGF-beta, but the response was sustained through 24 h. Collagenous protein synthesis in IGF-II- and TGF-beta-treated cells increased in parallel with increases in procollagen mRNA levels and was higher at 21 h for TGF-beta 1 and at 36 h for IGF-II. The difference in the time course and magnitude of change in type I procollagen mRNA levels in response to IGF-II and TGF-beta 1 suggests that these two growth factors work through distinct mechanisms that provide both a rapid transient response and a later sustained response in bone matrix biosynthetic activity.