Effect of IL‐1β, PGE2, and TGF‐β1 on the expression of OPG and RANKL in normal and osteoporotic primary human osteoblasts |
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Authors: | Susana Jurado Natalia Garcia‐Giralt Adolfo Díez‐Pérez Pedro Esbrit Guy Yoskovitz Lídia Agueda Roser Urreizti Lluís Pérez‐Edo Guillem Saló Leonardo Mellibovsky Susana Balcells Daniel Grinberg Xavier Nogués |
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Affiliation: | 1. Internal Medicine, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain;2. Laboratorio de Metabolismo Mineral y óseo, Fundación Jiménez Díaz (Capio Group), Madrid, Spain;3. Faculty of Biology, Department of Genetics, University of Barcelona, Barcelona, Spain;4. Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain;5. CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain;6. Department of Rheumatology, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain;7. Department of Traumatology and Orthopaedic Surgery, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain |
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Abstract: | 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 E2 (PGE2), 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 PGE2 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. |
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Keywords: | cytokines expression OPG osteoblasts protein RANKL |
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