RT Journal Article
T1 Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts.
A1 Manzano-Moreno, Francisco Javier
A1 Illescas-Montes, Rebeca
A1 Melguizo-Rodriguez, Lucia
A1 Costela-Ruiz, Victor J
A1 Garcia-Martinez, Olga
A1 Ruiz, Concepcion
A1 Ramos-Torrecillas, Javier
K1 bisphosphonates
K1 fibroblast
K1 gene expression
K1 jaw
K1 osteonecrosis
AB 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.
PB Ivyspring International Publisher
YR 2019
FD 2019-10-21
LK http://hdl.handle.net/10668/14832
UL http://hdl.handle.net/10668/14832
LA en
NO Manzano-Moreno FJ, Illescas-Montes R, Melguizo-Rodriguez L, Costela-Ruiz VJ, García-Martínez O, Ruiz C, et al.  Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts. Int J Med Sci. 2019 Oct 21;16(12):1534-1540
DS RISalud
RD Apr 7, 2025