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Prostaglandin mediated modulation of transforming growth factor‐β metabolism in primary mouse osteoblastic cells in vitro
Author(s) -
KleinNulend Jenneke,
Semeins Cornelis M.,
Burger Elisabeth H.
Publication year - 1996
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(199607)168:1<1::aid-jcp1>3.0.co;2-t
Subject(s) - prostaglandin e2 , endocrinology , medicine , transforming growth factor , prostaglandin , downregulation and upregulation , prostaglandin e , chemistry , endogeny , bone remodeling , catabolism , anabolism , metabolism , biology , biochemistry , gene
Prostaglandins and transforming growth factor‐β (TGF‐β) are both important local regulators of bone metabolism, but their actions on bone are complex. Prostaglandins mediate bone loss due to immobilization, but prostaglandin E 2 (PGE 2 ) treatment stimulates bone formation in vivo. TGF‐β may have both anabolic and catabolic effects on bone in vitro. In this study, we tested the effects of PGE 2 on TGF‐β release and on TGF‐β messenger RNA (mRNA) levels in neonatal mouse calvarial cell cultures. We also examined the relationship between endogenous prostaglandin production as a result of mechanical stress and the release of TGF‐β. Addition of PGE 2 (10 −8 − 10 −6 M) to the culture medium stimulated the release of TGF‐β peptide (active plus latent) after 24 and 48 h in a dose‐related manner. This upregulation was paralleled by an increased expression of TGF‐β mRNA levels. Mechanical stimulation by 1 h treatment with pulsating fluid flow (producing a shear stress of 0.5 ± 0.02 Pa at 5 Hz) resulted 1 h posttreatment in increased production of PGE 2 , prostaglandin I 2 (PGI 2 ), and prostaglandin F 2a . In addition, the release of TGF‐β activity but not TGF‐β peptide was decreased 24 h after PFF treatment. Addition of indomethacin, which blocks endogenous prostaglandin production, neutralized the effect of PFF treatment on TGF‐β activity, indicating that the effect of stress was mediated by endogenous prostaglandins. These results suggest that PGE 2 and other prostaglandins (probably PGI 2 and/or PGF 2a ) have opposite effects on TGF‐β metabolism in bone cells, as PGE 2 upregulates TGF‐β expression and synthesis while other prostaglandins downregulate TGF‐β activation. © 1996 Wiley‐Liss, Inc.