Fibroblast Growth Factor-2 Maintains the Differentiation Potential of Nucleus Pulposus Cells In Vitro

Abstract

The presence of FGF-2 during culture expansion of nucleus pulposus cells in monolayer can sustain a differentiated cell phenotype by maintaining responsiveness to TGF-beta1. Our results suggest that FGF-2 should be tested for its ability to maintain the reactivity of the nucleus pulposus cells to other morphogenic factors that may be used for cell-based transplantation therapy.

Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis

“…In the bovine IVD, we have found that bFGF released by chondrocytes after mechanical injury favors catabolism by stimulating MMP-13 production, inhibiting PG synthesis, and antagonizing the well-known cartilage anabolic activity of BMP7 (Li et al, 2008). Interestingly, Li et al (2008) found that bFGF stimulates an overall increase in sulfated PG synthesis in bovine NP tissue, similar to results reported by Tsai et al (2007). However, after normalization to cell number, both DMMB and 35 S-sulfate incorporation results suggested that, per cell, total PG accumulation and PG synthesis significantly decreased with bFGF stimulation in a dose-dependent manner (Li et al, 2008), suggesting a negative regulatory function of bFGF in spine cartilage homeostasis.…”

“…However, after normalization to cell number, both DMMB and 35 S-sulfate incorporation results suggested that, per cell, total PG accumulation and PG synthesis significantly decreased with bFGF stimulation in a dose-dependent manner (Li et al, 2008), suggesting a negative regulatory function of bFGF in spine cartilage homeostasis. In addition, while we (Li et al, 2008) and others (Tsai et al, 2007) have found that bFGF stimulates both collagen type I and II gene expression in the IVD, the ratio of collagen II:collagen I is significantly decreased in bovine IVD tissue (Li et al, 2008), presumably via increased collagen type I synthesis by fibrocytelike cells leading to the formation of fibrocartilage.…”

“…In lapine articular cartilage, bFGF introduced via gene transfer was found to increase cell proliferation both in vitro and in vivo, suggesting its potential for repair and regeneration of cartilage defects (Kaul et al, 2006). Due to its proliferative capacity, several studies have identified bFGF as an anabolic factor in chondrogenesis and ECM homeostasis (Thompson et al, 1991;Kaul et al, 2006;Tsai et al, 2007).…”

“…Previously, bFGF has been identified as an anabolic mediator of disc homeostasis via a bFGF-mediated stimulation of PG synthesis in a canine IVD tissue culture system (Thompson et al, 1991) and cell proliferation in rat discs (Nagano et al, 1995) and human discs (Doita et al, 1996). Recently, Tsai et al analyzed the effects of bFGF on bovine NP cell growth and differentiation cultured in monolayer and alginate and found that bFGF stimulated increased sulfated PG synthesis, lower aggrecan turnover, and differentiation of NP cell phenotype by maintaining responsiveness to TGF-β (Tsai et al, 2007).…”

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

“…2g-i). FGF-2 sustains the differentiated phenotype of cultured NP cells by maintaining their responsiveness to TGF-b [140]. FGF-2 also increases the numbers of inflammatory cells, including macrophages, lymphocytes, and fibroblasts in herniated disc and facilitates the resorption of material extruded into the epidural space [86].…”