Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts.

Abstract

The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10-5, 10-7, or 10-9 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of BPs at a dose of 10-9 M on the expression of FGF, CTGF, TGF-β1, TGFβR1, TGFβR2, TGFβR3, DDR2, α-actin, fibronectin, decorin, and elastin. Fibroblasts proliferation was significantly increased at the lowest dose (10-9M) of each BP but was not affected at the higher doses (10-5 and 10-7M). The proliferation increase may be related to the rise in TGF-β1 and TGFβR1 expression detected after the treatment of cells with 10-9M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased versus controls. The results of this in vitro study indicate that a very low BP dose (10-9 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation.

• Authors: Francisco Javier Manzano-Moreno, Rebeca Illescas-Montes, Lucia Melguizo-Rodriguez, Victor J Costela-Ruiz, Olga García-Martínez, Concepción Ruiz, Javier Ramos-Torrecillas
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 16 Issue 12 Pg. 1534-1540 ( 2019) ISSN: 1449-1907 [Electronic] Australia
• PMID: 31839740 (Publication Type: Journal Article)
• Copyright: © The author(s).

Chemical References

• Diphosphonates
• Zoledronic Acid
• Ibandronic Acid
• Alendronate

Topics

• Alendronate (pharmacology)
• Bisphosphonate-Associated Osteonecrosis of the Jaw (drug therapy, genetics, pathology)
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Diphosphonates (pharmacology)
• Fibroblasts (drug effects)
• Gene Expression Regulation (drug effects)
• Humans
• Ibandronic Acid (pharmacology)
• Jaw (drug effects, metabolism, pathology)
• Osteoblasts (drug effects)
• Real-Time Polymerase Chain Reaction
• Zoledronic Acid (pharmacology)