Gene. 2021 Feb 15;769:145253.doi:10.1016/j.gene.2020.145253. Epub 2020 Oct 22.

FN1 promotes chondrocyte differentiation and collagen production via TGF-β/PI3K/Akt pathway in mice with femoral fracture

Heli Zhang  1 Xue Chen  2 Pan Xue  2 Xinli Ma  3 Junfeng Li  4 Jun Zhang  5 Affiliations

Abstract

Fibronectin (FN) functions as a potent stimulator of osteogenic differentiation, and bone fracture healing. In FN family, FN1 acts as an interactive protein gene product to mediate chondrocyte adhesion. However, its effect on fracture healing remains elusive. Therefore, we aimed to investigate the involvement of FN1 in fracture healing. Hard callus formations were found at fracture site with thicker periosteum in lateral cortical bone area outside the fracture site in model mice. The decreased number of osteogenic cells in the middle of the callus region and increased extracellular matrix were suggestive of successful induction. Immunoblotting and RT-qPCR revealed that expression of FN1 was increased in tissues of fracture mice. As displayed by Safranin-fast green staining hematoxylin-eosin staining, the overexpression of FN1 at fracture site promoted osteoid formation and chondrocyte differentiation. The stimulating role of FN1 in collagen production was evidenced by increased levels of Col2, Col1, ColX, Osteonectin, and Osteocalcin and enhanced BMD, BV, BV/TV and Tb.Th values verified by immunoblotting and immunohistochemical staining. Additionally, the upregulation of FN1 contributed to promoted TGF-β, c-Caspase-9/t-Caspase-9 ratio and NF-κB p65 protein expression as well as lowered p-PI3K/PI3K and p-AKT/AKT ratios, implying the positive correlation between FN1 and the TGF-β/PI3K/Akt signaling pathway. The key findings of the present study provided evidence indicating that overexpression of FN1 contributes to fracture healing by activation of the TGF-β/PI3K/Akt signaling pathway.

Keywords: Chondrocyte; Collagen; FN1; Femoral fracture; Fracture healing; TGF-β/PI3K/Akt signaling pathway.

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