Conditioned Media from LPS-Activated Human Adipose-Derived Mesenchymal Stem Cells Enhances Bone Regeneration in Type 2 Diabetic Rats

Type 2 diabetes mellitus disrupts bone metabolism and impairs bone regeneration, making the bone repair in patients with type 2 diabetes mellitus become a great challenge. The aim of this study is to investigate the effect of conditioned media from LPS-activated human adipose-derived mesenchymal stem cells (LPS-CM) on bone regeneration in type 2 diabetic rats. Type 2 diabetic rats were successfully induced via a high-fat diet and low-dose streptozotocin intraperitoneal injection. After treatment with LPS-CM, the proliferation and migration of bone marrow-derived mesenchymal stem cells from type 2 diabetic rats (BMSCs) were significantly enhanced. In vitro osteogenic induction experiment showed that BMSCs treated with LPS-CM displayed increased ALP activity and calcium deposition. The beneficial effects of LPS-CM on osteogenic differentiation were also confirmed by elevated expression of osteogenesis-related genes including OCN, OPN, RUNX2, and Osx. Furthermore, in vivo study using a rat calvarial bone defect model revealed that LPS-CM had a better osteogenic capacity than conditioned media from unstimulated mesenchymal stem cells. These findings demonstrated that LPS-CM can enhance bone regeneration in type 2 diabetic rats by promoting the proliferation, migration and osteogenic differentiation of BMSCs, suggesting that LPS-CM may provide a promising route for bone repair in patients with type 2 diabetes mellitus.