Interactions of Growth Factors Present in Bone Matrix with Bone Cells: Effects on DNA Synthesis and Alkaline Phosphatase

Abstract

It has been shown that bone cells produce and secrete several growth factors (GFs) which are also found in the bone matrix. To investigate the role of these growth factors in bone cell metabolism, we compared the effects of different factors separately and in combination with respect to osteoblastic cell proliferation and differentiation. While basic fibroblast GF (FGF), transforming GF beta-1 (TGF beta), and platelet-derived GF (PDGF) enhance DNA synthesis, they had the opposite effect on alkaline phosphatase (ALP) activity in cell extracts: FGF, TGF beta, and PDGF inhibited cell ALP but strongly stimulated DNA synthesis. The IGFs had little effect on cell ALP but increased the release of ALP into the conditioned medium. In mitogenic tests of combinations of GFs, most had at least additive effects at low concentrations, and FGF, TGF beta, and IGF2 produced synergistic effects. Evidence is presented for (1) the modulation of the effects of one GF by the action of other GF, (2) synergistic interactions between FGF, TGF beta, and IGF2, and (3) a possible role for the observed interactions among GF for the mitogenic effect of human bone extract.

A new simplified technique for producing platelet-rich plasma: a short technical note

“…The effects of these growth factors on cell behavior and bone-healing sequences have been thoroughly studied [4,5,7,11,15,20,21].…”

“…Collagen and protein synthesis by osteoblasts is also stimulated by PDGF, but also requires the presence of IGF-I [7]. PDGF probably enhances the secretion of IGF-I by the osteoblasts and mesenchymal stem cells, which then accelerates the formation of a collagenous matrix [11]. PDGF also seems to enhance the activity of BMP in promoting cartilage and bone formation [10].…”

“…Further, TGF-β acts only locally, with no influence on bone formation at sites distant from its application [19]. Furthermore, multiple growth factors are present at the same time at the site of bone formation and have a synergistic effect on each other [11]. A study about growth factor interactions concluded that TGF-β, IGF-II, and FGF modify the activity of other growth factors and cytokines and actually have a synergistic effect in combination [11].…”

Do autologous growth factors enhance transforaminal lumbar interbody fusion?

“…Recent studies have reported the efficacy of bone morphogenetic protein (BMP) in facilitating spinal fusion [5]. The beneficial effects of platelet-derived growth factor (PDGF) on bone formation in vitro has also been described previously [9,10,18,20,22,34,36,37], while in vivo stimulation of bone formation by transforming growth factor-β (TGF-β) has been shown in animal models [20,30,33]. Both PDGF and TGF-β have mitogenic effects on fibroblasts, osteoblasts, and mesenchymal cells by the stimulation of DNA synthesis and cell replication [12].…”

“…One study [33]demonstrated that the effect of TGF-β is a local one, with no effects on bone formation at distant sites. Other authors have noted that multiple growth factors are present at the same time at the site of bone formation and have a synergistic effect on one another [22]. This led to the concept of providing high concentrations of growth factors at the actual site of fusion, in order to mimic the natural process of osteogenesis as closely as possible.…”