Avenanthramide C and chondroitin sulphate promote chondrogenic differentiation of adipose-derived mesenchymal stem cells

Loss of functional chondrocytes contributes to cartilage degeneration. Autologous transplantation of adipose-derived mesenchymal stem cells (ASCs) offers a promising approach for cartilage repair; however, current differentiation protocols remain suboptimal. To improve chondrogenic outcomes, we supplemented the standard Chondrocyte Differentiation Medium (CDM1) with Avenanthramide C (Avn C), a compound primarily known for its anti-inflammatory and chondroprotective activity. Unexpectedly, Avn C enhanced COL2A1 protein deposition, the primary collagen type that is cartilage tissue-specific. Co-administration of chondroitin sulphate (CS), a major extracellular matrix component, further elevated the expressions of important chondrogenic genes including AGGRECAN, SOX9, and LRP1. Proteomic analysis revealed increased secretion of SERPINs and complement proteins, known regulators of cartilage homeostasis and chondrocyte function, in the presence of Avn C and CS. This work identified Avn C (besides for chondroprotection) and CS as synergistic enhancers of chondrogenic differentiation in ASCs, as evidenced by the expression of articular cartilage–specific markers LRP1 and AGGRECAN, supporting their relevance for regenerative applications.