Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin.

ABSTRACT

A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-ß1), the most common growth factor used in chondrogenic induction medium. Herein, we directly compared the in vitro chondrogenic potency of TGF-ß1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7-14 days in medium supplemented with TGF-ß1, KGN, or both TGF-ß1 + KGN. Following 14 days of induction, micropellets exposed to TGF-ß1 alone or TGF-ß1 + KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-ß1 + KGN was used, GAG quantities were similar or slightly greater than the TGF-ß1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-ß1 + KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-ß1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering.