PMID- 32281654 OWN - NLM STAT- MEDLINE DCOM- 20210218 LR - 20210218 IS - 1943-3670 (Electronic) IS - 0022-3492 (Linking) VI - 91 IP - 12 DP - 2020 Dec TI - Inhibition of GDF11 could promote bone healing in the tooth extraction socket and facilitate mesenchymal stem cell osteogenic differentiation in T2DM pigs. PG - 1645-1652 LID - 10.1002/JPER.20-0011 [doi] AB - 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. CI - (c) 2020 American Academy of Periodontology. FAU - Wang, Shuyan AU - Wang S AD - Department of Oral Disease, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - Wang, Lei AU - Wang L AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - Shi, Shaojie AU - Shi S AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - Wang, Xingxing AU - Wang X AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - He, Chunxia AU - He C AD - Institute of Basic Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, China. FAU - Yuan, Lijuan AU - Yuan L AD - Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China. FAU - Ding, Feng AU - Ding F AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - Song, Yingliang AU - Song Y AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. FAU - Zhang, Sijia AU - Zhang S AUID- ORCID: 0000-0002-7549-782X AD - Department of Implant Dentistry, School of Stomatology, The Air Force Medical University, Xi'an, China. AD - Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi'an, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200508 PL - United States TA - J Periodontol JT - Journal of periodontology JID - 8000345 RN - 0 (Bone Morphogenetic Proteins) RN - 0 (GDF11 protein, human) RN - 0 (Growth Differentiation Factors) SB - IM MH - Animals MH - Bone Morphogenetic Proteins MH - Cell Differentiation MH - *Diabetes Mellitus, Type 2 MH - Growth Differentiation Factors MH - Humans MH - *Mesenchymal Stem Cells MH - Osteogenesis MH - Swine MH - Tooth Extraction MH - Tooth Socket MH - X-Ray Microtomography OTO - NOTNLM OT - bone regeneration OT - growth factors OT - mesenchymal stem cells OT - tooth socket OT - type 2 diabetes mellitus EDAT- 2020/04/14 06:00 MHDA- 2021/02/20 06:00 CRDT- 2020/04/14 06:00 PHST- 2020/01/09 00:00 [received] PHST- 2020/02/29 00:00 [revised] PHST- 2020/03/18 00:00 [accepted] PHST- 2020/04/14 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/04/14 06:00 [entrez] AID - 10.1002/JPER.20-0011 [doi] PST - ppublish SO - J Periodontol. 2020 Dec;91(12):1645-1652. doi: 10.1002/JPER.20-0011. Epub 2020 May 8.