Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts
Metadata
Show full item recordAuthor
Manzano Moreno, Francisco Javier; Illescas Montes, Rebeca; Melguizo Rodríguez, Lucía Raquel; Costela Ruiz, Víctor Javier; García Martínez, Olga; Ruiz Rodríguez, Concepción; Ramos Torrecillas, JavierEditorial
Ivyspring International Publisher
Materia
Bisphosphonates Osteonecrosis Fibroblast Gene expression
Date
2019-10-21Referencia bibliográfica
Manzano, F. J. (2019). Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts. International Journal of Medical Sciences, 16(12), 1534-1540.
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.