Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts Manzano Moreno, Francisco Javier Illescas Montes, Rebeca Melguizo Rodríguez, Lucía Raquel Costela Ruiz, Víctor Javier García Martínez, Olga Ruiz Rodríguez, Concepción Ramos Torrecillas, Javier Bisphosphonates Osteonecrosis Fibroblast Gene expression 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. 2019-12-12T10:42:06Z 2019-12-12T10:42:06Z 2019-10-21 journal article 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. http://hdl.handle.net/10481/58272 10.7150/ijms.36994 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Ivyspring International Publisher