Functional differences of Toll‐like receptor 4 in osteogenesis, adipogenesis and chondrogenesis in human bone marrow‐derived mesenchymal stem cells

Multipotent human bone marrow-derived mesenchymal stem cells (hMSCs) are promising candidates for and cartilage regeneration. Toll-like receptor 4 (TLR4) is expressed by hMSCs a both exogenous endogenous danger signals. TLRs have been shown to possess functional differences based on the species (human or mouse) they isolated from therefore, effects of knockdown TLR4 were evaluated in humans during differentiation MSCs into bone, fat chondrocyte vitro. We investigated expression profile three different lineages days 7, 14 21 assessed potential presence lipopolysaccharide (LPS, as an agonist) fibronectin fragment III-1c (FnIII-1c, agonist). increased following induction hMSC all lineages. Alkaline phosphatase activity revealed that FnIII-1c accelerated calcium deposition day whereas LPS 14. Chondrogenesis LPS; however, acted reducer late stage. silencing led decreased osteogenesis adipogenesis. Furthermore, Wnt5a was inversely related chondrogenesis stage differentiation. suggest understanding functionality (in pathogen stress signal) would be useful MSC-based treatments.