IL-17 alters MSC cell niche towards osteogenesis cooperated with osteocytes

Abstract

Objectives: Bone remodelling is a strictly regulated dynamic process of bone formation and resorption. IL-17 critically orchestrates the activation and differentiation of both osteoblasts and osteoclasts. Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that may likely influence how MSCs differentiate into bone precursors. Osteocytes are involved in the bone adaptation, and their role in regulating the osteogenic differentiation of MSCs remains unclear. This study investigated the roles of IL-17 in various stages of osteoblastic differentiation, and explored osteocyte-specific signalling pathway in the osteogenesis of MSCs. Methods: We first examined whether IL-17 induced the osteogenic differentiation of MSCs, osteoblasts and osteocytes. Additionally, the role of biochemical signalling from osteocytes and osteoblasts was assessed via transwell co-culture experiments, to understand how they may directly influence differentiation of MSCs with or without IL-17. The reasons for synergistic effects of osteocytes and IL-17 were investigated using signalling inhibitors and neutralizing antibodies in stem cell niche. Results: We found that IL-17 induced the osteogenesis of MSCs, which was attenuated by IL-17RA blocking. Additionally, osteocytes were more influential than osteoblasts in stimulating osteogenesis in MSCs with IL-17. Furthermore, inflammatory factors IL-6 and IL-1β played an important role in IL-17-dependent differentiation, via activating ERK1/2, AKT and STAT3 signalling pathways in MSC niche. Conclusions: The present study confirms a synergistic action of osteocytes and IL-17 in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This finding provides important insights into the mechanisms within the native stem cell niche to stimulate osteogenic differentiation, and suggests a possible role of IL-17 in bone tissue engineering.