The Function And Its Underlying Mechanism Of FPH2 Regulating Chondrocyte Phenotype Maintenance

Osteoarthritis is now the most widespread degenerative joint disease and is the leading cause of disability,which puts a heavy burden on society.As our understanding of the pathogenesis of osteoarthritis is still unclear,there is still a lack of effective treatment at this stage.Articular cartilage defect is an important pathological feature in the early stage of osteoarthritis.Regeneration of cartilage defects is an important means to prevent the development of OA.Chondrocyte-based therapies have been reported to show good repair effects in the clinic,but chondrocytes still present significant challenges in quality control and quantitative expansion.The aim of this study was to screen a small molecule drug for maintaining the chondrocyte phenotype during efficient expansion of seed cells,moreover,to verify the drug effects and uncover the molecular mechanism of chondrocyte phenotype changes with the stimulation of this small molecule drug.It is expected to find new drug targets for the treatment of osteoarthritis.We first screened and found the FPH2 small molecule drug by high-throughput Col2-pd2 EGFP system,and studied its function in chondrocyte culture.With RNA-seq results and bioinformatics methods,the potential molecular mechanism of FPH2 wasillustrated.In addition,the sustained release of FPH2 was proved to effectively maintain cartilage homeostasis in rat partial thickness cartilage defects.Our study found that: 1)FPH2 shows that low dose can promote the proliferation of chondrocytes and C3 H cells in vitro;2)FPH2 can promote the synthesis of cartilage matrix and maintain chondrocyte phenotype while promoting proliferation;3)The results of RNA-seq showed that the pathways of proliferation,metabolism and cartilage matrix synthesis were up-regulated after drug treatment;4)Sustained release of FPH2 can effectively delay the degeneration of cartilage in the rat cartilage defect model.In summary,we found that FPH2 can promote chondrocyte proliferation,maintain chondrocyte phenotype,help cartilage defect regeneration and prevent further cartilage degeneration.