Abstract:The differentiation regulation and cytotherapy based on stem cells will provide useful new therapeutic strategy for related bone and joint disease. For the last several years， we found that Dexamethasone (Dex) shifts bone marrow mesenchymal stem cells (BMMSCs) from osteoblasts to adipocytes by C/EBPα promoter methylation. Wnt/β-catenin pathway activation by LiCl rescues the effect of Dex on C/EBPα promoter methylation and osteoblast/adipocyte balance， thus providing a useful therapeutic target for Dex-induced osteoporosis. We found an interesting phenomenon that articular cartilage stem cells (ACSCs) were activated and exhibited a transient proliferative response in early osteoarthritis (OA) as an initial attempt for self-repair， whereas IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs. The NF-κB pathway inhibitor rescued the ACSCs chondrogenesis， induced cartilage regeneration， and protected articular cartilage from injury. We developed a new safety， effectiveness， and minimal invasiveness clinical cytotherapy method based on enriched BMSCs combined with porous β-tricalcium phosphate (β-TCP). The cytotherapy could promote bone and cartilage repair and regeneration， it avoids some ethical problems associated with cell expansion and becomes both less expensive and more convenient for clinical usage.