Kartogenin, transforming growth factor-ß1 and bone morphogenetic protein-7 coordinately enhance lubricin accumulation in bone-derived mesenchymal stem cells.

ABSTRACT

Osteoarthritis, a common joint degeneration, can cause breakdown of articular cartilage with the presence of lubricin metabolic abnormalities. Lubricin is a multi-level chondroprotective mucinous glycoprotein in articular joints. Joint defect and infection is elevated and accompanied by accelerated cartilage lesions involving degradation and loss of lubricin. However, a novel, heterocyclic compound called kartogenin (KGN) was discovered to stimulate chondrogenic differentiation of bone-derived mesenchymal stem cells (BMSCs). And the synergistic effect of transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7) could provoke lubricin accumulation. This paper attempted to explore the connection between accumulation of lubricin and the effect of TGF-ß1, BMP-7 and/or KGN. Hence, we investigated the expression and secretion of lubricin in BMSCs treated with different combinations of TGF-ß1, BMP-7, and/or KGN. Using an in vitro BMSCs system, we observed the content of lubricin from BMSCs treated with TGF-ß1, BMP-7, and KGN was the highest at both the protein level and the gene level. The accumulation of lubricin was enhanced coordinately by the increase of synthesis and decrease of degradation possibly via c-Myc and adamts5 pathway. These results further suggested that supplementation of the defect parts with lubricin by using growth factors and small molecules showed a promising potential on preventing joint deterioration in patients with acquired or genetic deficiency of lubricin in the future of regenerative medicine.