IGF-I induces adipose derived mesenchymal cell chondrogenic differentiation in vitro and enhances chondrogenesis in vivo

Abstract

Recent studies have demonstrated that insulin-like growth factor-1 (IGF-I) modulates bone mesenchymal stem cell chondrogenic differentiation independent of transforming growth factor beta (TGF-β) signaling in vitro. However, it is unclear whether IGF-I can solely modulate human adipose-derived mesenchymal cell (hAMC) chondrogenic differentiation, or whether it has additive effects with TGF-β1 to induce chondrogenic differentiation in vitro and development of mature cartilage in vivo. We investigated the effect of IGF-I on the induction of hAMC chondrogenic differentiation in the presence or absence of transforming growth factor beta 1 (TGF-β1) in vitro, and chondrogenesis of the induced hAMC in vivo. The results showed that IGF-I alone induced collagen type II, aggrecan, and Sox9 mRNA expression and collagen type II and aggrecan proteins expressions in hAMCs. Notably, there was greater mRNA expression of collagen type II, aggrecan and Sox9, and greater protein expression of collagen type II and aggrecan following TGF-β1 + IGF-I treatment, compared to either TGF-β1 or IGF-I-treated hAMCs. These results were confirmed in cartilage tissues derived from induced hAMCs. These findings indicate that IGF-I alone has the ability to induce chondrogenic differentiation and has additive effects with TGF-β1 to induce chondrogenic differentiation in vitro and in vivo.

Trypsin Pre‐Treatment Combined With Growth Factor Functionalized Self‐Assembling Peptide Hydrogel Improves Cartilage Repair in Rabbit Model

“…Surprisingly, no significant main effects of HB‐IGF‐1 on proteoglycan deposition were observed. Insulin Growth Factor‐1 has been studied in cartilage repair and has been reported both in vitro and in vivo to significantly improve chondrogenesis and cartilage integration . Our group has reported that HB‐IGF‐1 is strongly retained in articular cartilage post‐intra‐articular injection and leads to sustained proteoglycan biosynthesis in cartilage explants .…”

“…Insulin Growth Factor-1 has been studied in cartilage repair and has been reported both in vitro and in vivo to significantly improve chondrogenesis and cartilage integration. [26][27][28][29] Our group has reported that HB-IGF-1 is strongly retained in articular cartilage post-intra-articular injection 30 and leads to sustained proteoglycan biosynthesis in cartilage explants. 31 Interestingly, an in vitro kinetics study showed that 84% of the HB-IGF-1 that was premixed into a KLD hydrogel was released within the first four days of culture 4 ; however, this HB-IGF-1 seems to be bound by surrounding cartilage annuli instead of being released in the media 14 .…”

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

“…Therefore, different receptor and ligand combinations can cause variable signaling outcomes, especially in stem cells. Few studies have been reported on the effects of IGF-1 on the growth, differentiation, and migratory capacity of mesenchymal stem cells [36, 38, 47]; however, the expression of different IGF receptors, insulin receptors, and hybrid receptors and their relative roles in pluripotency and differentiation have not been well studied.…”

“…Although TGF- β signaling is known to be important for chondroinductive differentiation from MSCs, more studies are showing that IGF-1 can regulate MSC chondrogenesis independent of TGF- β . In one study, IGF-1 can induce chondrogenic differentiation from adipose-derived MSCs with increased collagen type II, Aggrecan, and SOX9 levels [38]. Similarly, IGF-1 induced the chondrogenic potential of BM-derived MSCs stimulating proliferation, regulating apoptosis, and inducing expression of chondrogenic markers [119].…”

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

“…However, results are mixed with some studies reporting ASCs have inferior chondrogenic potential in comparison to BM-MSCs (Afizah et al, 2007), whilst others not finding any significant difference between the two cell types (Ronziere et al, 2010). Various growth factors have been shown to promote in vitro cartilage formation of ASCs, amongst them the effectiveness of TGF-β1, IGF-1 (Zhou et al, 2016), and BMP-6 (Hennig et al, 2007) has been well established. Besides the soluble chemical regulators of cartilage formation, a wide range of chondrogenesis promoting scaffolds have been developed and introduced.…”