Abstract
Systematic bone loss is commonly complicated with inflammatory bowel diseases (IBDs) with unclear pathogenesis and uncertain treatment. In experimental colitis mouse models established by dextran sulfate sodium and IL-10 knockout induced with piroxicam, bone mass and quality are significantly decreased. Colitis mice demonstrate a lower bone formation rate and fewer osteoblasts in femur. Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis mice tend to differentiate into adipocytes rather than osteoblasts. Serum from patients with IBD promotes adipogenesis of human BMSCs. RNA sequencing reveals that colitis downregulates Wnt signaling in BMSCs. For treatment, exosomes with Golgi glycoprotein 1 inserted could carry Wnt agonist 1 and accumulate in bone via intravenous administration. They could alleviate bone loss, promote bone formation, and accelerate fracture healing in colitis mice. Collectively, BMSC commitment in inflammatory microenvironment contributes to lower bone quantity and quality and could be rescued by redirecting differentiation toward osteoblasts through bone-targeted drug delivery.