Recombinant Human Fibroblast Growth Factor-2(SVS Institute of Dental Sciences)

Mechanical stimuli serve as crucial regulators of bone mass, promoting bone formation. However, the molecular mechanisms governing how mesenchymal stem cells (MSCs) respond to mechanical cues during their differentiation into osteogenic cells remain elusive. In this study, we found that cyclic stretching enhances MSC proliferation but does not increase the expression of osteoblast-related genes. We further revealed that this proliferative effect is mediated by fibroblast growth factor 2 (FGF-2), synthesized by MSCs in response to mechanical stress. Cell proliferation induced by cyclic stretching was inhibited upon the addition of either U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK), or early growth response 1 (EGR1)-targeting small-hairpin RNA (shRNA), indicating the involvement of the extracellular signal-regulated kinase (ERK)/EGR1 signaling pathway. Osteoblast differentiation, evaluated through ALP activity, osteoblast-related gene expression, and mineralization, was stimulated by recombinant human FGF-2 (rhFGF-2) when applied during the proliferation phase, but not when applied during the differentiation stage alone. Our results suggest that FGF-2 indirectly promotes osteoblast differentiation as a downstream effect of stimulating cell proliferation. For the first time, we demonstrate that cyclic stretching induces MSCs to produce FGF-2, which in turn encourages cell proliferation through an autocrine/paracrine mechanism, consequently leading to osteoblast differentiation.

Growth factors have been used with success in periodontal regeneration, especially in intrabony defects. Among those, the recombined form of fibroblast growth factor-2 (rhFGF-2) has been also examined.

To address the outcomes of periodontal regeneration using rhFGF-2 alone or in combination with bone substitutes primarily in terms of Radiographic Bone Fill (RBF%) and secondary Probing Pocket Depth (PPD), and Probing Attachment Levels (PAL).

A search in MEDLINE and EMBASE using the Ovid interface was conducted from 2000 up to and including the 12th of November 2022. Starting from the initially identified 1289 articles, 34 studies were selected for further analysis. Following the full-text screening, 7 of the 34 studies met the inclusion criteria and thus were included in the systematic review after assessing their quality according to the Newcastle-Ottawa scale (NOS). Clinical and radiographic results (bone gain, pocket depth, and clinical attachment level) after the application of FGF-2 alone or in combination with different carriers were studied in patients with intrabony defects of at least one wall and pocket depth greater than 4 mm.

Primary outcomes: RBF% was higher in studies using a combination of rhFGF-2 and bone substitutes (74.6 ± 20.0%) compared to others using the specific growth factor alone or negative controls (22.7 ± 20.7%). In terms of secondary outcomes, the analysis failed to show an additional benefit from the use of the rhFGF-2 alone or in combination with bone substitutes.

rhFGF-2 can improve RBF% in the treatment of periodontal defects, especially when it is used in combination with a bone substitute.