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What makes an accurate and reliable subject-specific finite element model? A case study of an elephant femur

2014; Royal Society; Volume: 11; Issue: 99 Linguagem: Inglês

10.1098/rsif.2014.0854

1742-5689

Olga Panagiotopoulou, Simon Wilshin, Emily J. Rayfield, Sandra J. Shefelbine, John R. Hutchinson,

Hip disorders and treatments

Simple Summary:The cartilage-to-bone transition is an essential process in healthy bone development and repair.Our previous work has shown that when the cells found within the human periosteum (the membrane surrounding the bone) are cultured in human serum (HS) as opposed to the standard animal serum (FBS), these cells have greater bone-forming capacity as assessed in an ectopic assay in nude mice.What is not understood is the molecular interactions that permitted this enhanced biological potency.Herein, virtual networks are created to identify the key proteins driving increased bone formation from these cells.Key signalling factors were identified through a network analysis, where FGFR3 was pinpointed as a major differential regulator between cells grown in HS and cells grown in FBS.This analysis was validated through an analysis of human-derived periosteal progenitor cells (PDCs) containing a constitutively active (ca) FGFR3.Following removal and analysis, we found that the FGFR3-ca cells that were implanted on bone void filler scaffolds in mice had an abundance of bone and cartilage that were present compared to the scaffold containing normal/healthy cells.This suggests that these cells were undergoing enhanced cartilage-to-bone transitions and that this protein may be a potentially novel therapeutic target for diseases where the cartilage-to-bone transition is affected such as during poor fracture healing.