Recombinant transforming growth factor type beta 3: biological activities and receptor-binding properties in isolated bone cells.
We have recently cloned the cDNA for transforming growth factor type beta 3 (TGF-beta 3), a new member of the TGF-beta gene family. We examined the biological effects of recombinant TGF-beta 3 protein in osteoblast-enriched bone cell cultures. In this report we demonstrate that TGF-beta 3 is a potent regulator of functions associated with bone formation, i.e., mitogenesis, collagen synthesis, and alkaline phosphatase activity. In a direct comparison between TGF-beta 3 and TGF-beta 1, TGF-beta 3 appeared to be three- to fivefold more potent than TGF-beta 1. Our cross-linking experiments with iodinated TGF-beta showed that in osteoblast-enriched bone cell cultures, both TGF-beta 3 and TGF-beta 1 associated with the same three cell surface binding sites. Scatchard analysis of receptor competition studies indicated the presence of high-affinity binding sites for TGF-beta 3 in the picomolar range. TGF-beta 3 showed an approximately fourfold-higher apparent affinity than TGF-beta 1 in overall binding.
ten Dijke
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P
Oncogene Science Inc., Manhasset, New York 11030.
Iwata
K K
KK
Goddard
C
C
Pieler
C
C
Canalis
E
E
McCarthy
T L
TL
Centrella
M
M
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection; D015291:Transforming Growth Factors / Q000378:metabolism / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D015291:Transforming Growth Factors; D003094:Collagen; D000469:Alkaline Phosphatase