Inhibition of GDF11 could promote bone healing in the tooth extraction socket and facilitate mesenchymal stem cell osteogenic differentiation in T2DM pigs

Background Growth differentiation factor 11 (GDF11) might be a key factor responsible for the weakening of mesenchymal stem cell (MSC) osteogenic differentiation in tooth extraction sockets in patients with type 2 diabetes mellitus (T2DM). This study aimed to confirm that inhibition of GDF11 could promote bone healing in tooth extraction sockets and facilitate MSC osteogenic differentiation under T2DM conditions. Methods Three streptozotocin-induced T2DM pig models and two control pig models were established. The T2DM pigs were treated with an intrasocket injection of GDF11 inhibitor in the left mandible, whereas the right side was maintained for natural healing. The postextraction socket healing of the T2DM pigs was compared with that of nondiabetic controls. Healing was quantitatively verified by microcomputed tomography, and the GDF11 expression level was detected. MSCs from T2DM pig sockets were cultured and treated with a GDF11 inhibitor. The osteogenic differentiation ability of MSCs was also compared among groups. Results The expression of GDF11 in the tooth extraction sockets from T2DM pigs increased significantly post extraction. Bone healing was promoted by periodic injection of the GDF11 inhibitor into the extraction sockets of T2DM pigs. Furthermore, the osteogenic differentiation ability of T2DM-MSCs was improved in pigs treated with the GDF11 inhibitor. Conclusions GDF11 inhibition could promote bone healing in the tooth extraction socket and facilitate MSC osteogenic differentiation under T2DM conditions. GDF11 could be a potential therapeutic target for undesirable alveolar bone healing in T2DM patients.