LncRNA NKILA integrates RXFP1/AKT and NF-κB signalling to regulate osteogenesis of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are previously found to have potential capacity to differentiate into osteocytes when exposed to specific stimuli. However, the detailed molecular mechanism during this progress remains largely unknown. In the current study, we characterized the lncRNA NKILA as a crucial positive regulator for osteogenesis of MSCs. NKILA attenuation significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. More interestingly, we defined that NKILA is functionally involved in the regulation of RXFP1/PI3K-AKT and NF-κB signalling. Knockdown of NKILA dramatically down-regulates the expression of RXFP1 and then reduces the activity of AKT, a downstream regulator of RXFP1 signalling which is widely accepted as an activator of osteogenesis. Moreover, we identify NF-κB as another critical regulator implicated in NKILA-mediated osteogenic differentiation. Inhibition of NF-κB can induce the expression of RUNX2, a master transcription factor of osteogenesis, in a HDAC2-mediated deacetylation manner. Thus, this study illustrates the regulatory function of NKILA in osteogenesis through distinct signalling pathways, therefore providing a new insight into searching for new molecular targets for bone tissue repair and regeneration.

Keywords: AKT; NF-κB; NKILA; RXFP1; osteogenic differentiation.