Insulin‐like growth factor‐1 (IGF‐1) enhances the osteogenic activity of bone morphogenetic protein‐6 (BMP‐6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF‐1 is combined with BMP‐2

Abstract

Bone morphogenetic protein-2 (BMP-2) is widely used in orthopedic surgery and bone tissue engineering because of its strong osteogenic activity. However, BMP-2 treatments have several drawbacks and many groups are actively exploring alternatives. Since BMP-6 has been demonstrated to be more osteoinductive, its use, either alone or together with other growth factors, might be an interesting option. In this work, we have compared the effect of BMP-2, BMP-6, or insulin-like growth factor-1 (IGF-1), either alone or in combination. Murine preosteoblasts were treated with 15 nM IGF-1 and/or 6 nM BMP-2 or -6 and the expression of osteogenic marker genes, proliferation, and alkaline phosphatase (ALP) activity in vitro were analyzed. The results showed that IGF-1 greatly enhanced the BMP-induced osteogenic differentiation of these cells in general and that the ALP activity in the cultures was higher when the combination was made with BMP-6 than with BMP-2. Furthermore, we tested the osteogenic potential of these treatments in vivo by loading 25 pmoles of IGF-1 and/or 10 pmoles of BMP-2 or -6 onto absorbable collagen sponges and implanting them into an ectopic bone formation model in rats. This study revealed that only BMP-6 was able to induce bone formation at the used dose and that the addition of IGF-1 contributed to an increase of the mineralization in the implants. Hence, the combination of BMP-6 with IGF-1 might be a better alternative than BMP-2 for orthopedic surgery or bone tissue engineering approaches. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1867-1875, 2017.

Combined treatment with electrical stimulation and insulin-like growth factor-1 promotes bone regeneration in vitro

“…Some studies indicated that IGF-1 is an important growth factor that can stimulate bone regeneration by enhancing osteoblast proliferation, bone matrix synthesis, osteoblastic gene expression, ALP activity and mineralization[ 15 , 29 – 33 ]. However, some recent studies showed that IGF-1 alone does not improve osteogenic proliferation[ 23 ], ALP activity[ 34 ], osteogenic differentiation[ 22 ] and mineralization[ 35 ]. We speculated that IGF-1 has a dose-dependent effect on osteogenesis, and different IGF-1 doses may lead to different levels of osteoblastic proliferation or differentiation.…”

The roles of signaling pathways in bone repair and regeneration

“…Additionally, IGF‐1 in combination with BMP‐ 2 have a stimulatory effect on the proliferation and osteogenic differentiation of stem cells derived from adipose tissue (Elias, ). Another study revealed that the combination of BMP‐6 with IGF‐1 might be a better alternative than BMP‐2 for inducing bone formation and increase in mineralization in the implants in orthopedic surgery or bone tissue engineering approaches (Rico‐Llanos, Becerra, & Visser, ). Results of a randomized controlled clinical study showed that combined use of VEGF and IGF‐I in conjunction with Polylactide‐Polyglycolide Acid (PLGA) membrane and β‐Tricalcium Phosphate (β‐TCP) osseous graft resulted in enhanced clinical outcomes in terms of pocket reduction, clinical attachment Level gain and bone fill as compared to VEGF and IGF‐I used alone (Devi & Dixit, ).…”

Calvarial Versus Long Bone: Implications for Tailoring Skeletal Tissue Engineering

“…When 10 pmole of BMP-2 or BMP-6 was administered, bone formation was observed in BMP-6 groups, indicating that BMP-6 may be a superior alternative than BMP-2 for inducing bone formation. 141 This is crucial as supraphysiological administration of BMP-2 has been reported to cause life-threatening cervical spine swelling. 142 PTH and PTH-related peptide (PTHrP), including their analogs, such as Teriparatide (shares the first 1-34 amino acid residues of PTH) and Abaloparatide (shares the first 1-22 amino acid residues of PTHrP), as well as humanized monoclonal antibodies, such as Romosozumab (targets Sclerostin, whose production is normally inhibited by PTH), have been widely investigated for their use in bone anabolic therapy.…”