Abstract
•High glucose inhibits proliferation and osteogenic differentiation of PDLSCs.•Autophagy affects the osteogenic differentiation of PDLSCs under high glucose.•Upregulating autophagy preserves the activity of PDLSCs in diabetic rats.•Upregulating autophagy improves periodontal trauma healing in diabetic rats.
To investigate how a high glucose environment influences the osteogenic ability of periodontal ligament stem cells (PDLSCs) and the function of autophagy in this process, we explored whether the osteogenic ability of PDLSCs could be protected by autophagy.
PDLSC proliferation and osteogenesis were evaluated by CCK-8 and western blotting under gradient glucose conditions. The Autophagy RT2 Profiler PCR Array was used to screen autophagy-related mRNA expression during PDLSC osteoblastic differentiation on 5.5 mM + osteogenic induction (OI) medium or 25 mM + OI medium on day 3. Autophagy was regulated by an inducer (rapamycin) and inhibitor (bafilomycin) to investigate its protective effects on PDLSCs. A periodontal trauma model was established in diabetic rats to verify the effects of enhanced autophagy activity on PDLSCs.
A high glucose concentration (25 mM) impeded PDLSC proliferation on day 1, and compared with the control condition, high glucose also decreased the osteogenic ability of PDLSCs. The Autophagy RT2 Profiler PCR Array showed obvious fluctuations in many autophagy-related genes, such as ULK1 (9.27), MTOR (3.15), MAP1LC3B (4.22), GABARAPL1 (7.09), ATG10 (6.5), AMPK14 (4.47), WIPI1 (3.29), and IGF1 (24.65). Compared with the control condition, an autophagy inducer or inhibitor markedly impaired or enhanced osteogenic differentiation in cells. The diabetic rat periodontal trauma model demonstrated that periodontium tissue partly recovered in the autophagy-enhanced cell injection diabetic rat group.
High glucose inhibited the activity of PDLSCs, and regulating autophagy protected cell function. Upregulating autophagy partially reversed the adverse effect of high glucose conditions on PDLSCs.