Osteoarthritis (OA) is the most prevalent chronic joint disease that affects a majority of the elderly. Chondrogenic progenitor cells (CPCs) reside in late stage OA cartilage tissue, producing a fibrocartilagenous extra-cellular matrix and can be manipulated in-vitro, to deposit proteins of healthy articular cartilage. CPCs are under control of SOX9 and RUNX2 and in order to enhance their chondrogenic potential, we found that RUNX2 plays a pivotal role in chondrogenesis. In another approach, CPCs carrying a knockout of RAB5C, a protein involved in endosomal trafficking, demonstrated elevated expression of various chondrogenic markers including the SOX trio and displayed an increased COL2 deposition, whereas no changes of COL1 deposition was observed. We report RAB5C as an attractive target for future therapeutic approaches to increase the COL2 content in the diseased joint.