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Effects of transforming growth factor α and interleukin‐1 on DNA synthesis, collagen synthesis, procollagen mRNA levels, and prostaglandin E 2 production in cultured fetal rat calvaria
Author(s) -
Hurley Marja M.,
Fall Pamela,
Harrison John R.,
Petersen Don.,
Kream Barbara E.,
Raisz Lawrence G.
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040512
Subject(s) - calvaria , dna synthesis , procollagen peptidase , endocrinology , medicine , prostaglandin e , prostaglandin , prostaglandin e2 , transforming growth factor , alpha (finance) , collagenase , biology , messenger rna , microbiology and biotechnology , chemistry , in vitro , biochemistry , enzyme , gene , construct validity , nursing , patient satisfaction
Transforming growth factor α (TGF‐α) and interleukin‐1 (IL‐1) have been shown to affect bone metabolism in vitro by prostaglandin‐dependent and PG‐independent mechanisms. We assessed the effects of the combination of these two agents on [ 3 H]thymidine (TdR) incorporation into DNA, DNA content, [ 3 H]proline incorporation into collagenase‐digestible (CDP), noncollagen protein (NCP), and PGE 2 production in 21 day fetal rat calvaria cultured for 24–96 h. We also determined whether TGF‐α plus IL‐1 altered procollagen mRNA levels at 96 h. TGF‐α, 1–30 ng/ml, produced a 41–59% increase in TdR incorporation into DNA, but the effect was partially blocked by human recombinant IL‐1. At 96 h TGF‐α alone or in combination with IL‐1 significantly increased the DNA content of calvaria. At 96 h, TGF‐α inhibited CDP labeling and the addition of IL‐1 further enhanced this inhibitory effect. The enhanced inhibitory effect of TGF‐α plus IL‐1 on collagen synthesis was associated with a synergistic increase in prostaglandin accumulation in the medium. Addition of indomethacin blocked PGE 2 accumulation and partially reversed the inhibitory effect of TGF‐α alone or in combination with IL‐1 on collagen synthesis. TGF‐α decreased procollagen mRNA levels by 55%, but the combination of TGF‐α plus IL‐1 decreased procollagen mRNA levels by 82%. Our results show that TGF‐α and IL‐1, which are both produced by certain tumors as well as activated macrophages, appear to act synergistically to increase prostaglandin synthesis and inhibit collagen synthesis in vitro. Thus these agents may have a regulatory role on bone formation in vivo.