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Effect of IL‐1β, PGE 2 , and TGF‐β1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts
Author(s) -
Jurado Susana,
GarciaGiralt Natalia,
DíezPérez Adolfo,
Esbrit Pedro,
Yoskovitz Guy,
Agueda Lídia,
Urreizti Roser,
PérezEdo Lluís,
Saló Guillem,
Mellibovsky Leonardo,
Balcells Susana,
Grinberg Daniel,
Nogués Xavier
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22538
Subject(s) - rankl , endocrinology , medicine , bone resorption , transforming growth factor , bone remodeling , cytokine , osteoclast , osteoporosis , chemistry , osteoblast , activator (genetics) , receptor , in vitro , biochemistry
The RANKL / RANK / OPG pathway is essential for bone remodeling regulation. Many hormones and cytokines are involved in regulating gene expression in most of the pathway components. Moreover, any deregulation of this pathway can alter bone metabolism, resulting in loss or gain of bone mass. Whether osteoblasts from osteoporotic and nonosteoporotic patients respond differently to cytokines is unknown. The aim of this study was to compare the effect of interleukin (IL)‐1β, proftaglandin E 2 (PGE 2 ), and transforming growth factor‐β1 (TGF‐β1) treatments on OPG and RANKL gene expression in normal (n = 11) and osteoporotic (n = 8) primary osteoblasts. OPG and RANKL mRNA levels of primary human osteoblastic (hOB) cell cultures were assessed by real‐time PCR. In all cultures, OPG mRNA increased significantly in response to IL‐1β treatment and decreased in response to TGF‐β1 whereas PGE 2 treatment had no effect. RANKL mRNA levels were significantly increased by all treatments. Differences in OPG and RANKL responses were observed between osteoporotic and nonosteoporotic hOB: in osteoporotic hOB, the OPG response to IL‐1β treatment was up to three times lower ( P = 0.009), whereas that of RANKL response to TGF‐β1 was five times higher ( P = 0.002) after 8 h of treatment, as compared with those in nonosteoporotic hOBs. In conclusion, osteoporotic hOB cells showed an anomalous response under cytokine stimulation, consistent with an enhanced osteoclastogenesis resulting in high levels of bone resorption. J. Cell. Biochem. 110: 304–310, 2010. © 2010 Wiley‐Liss, Inc.