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

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-beta) 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-beta 1 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-beta 1) 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-beta 1 + IGF-I treatment, compared to either TGF-beta 1 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-beta 1 to induce chondrogenic differentiation in vitro and in vivo.