Local Concentrations of TGF-β1 and IGF-1 Appear Determinant in Regulating Bone Regeneration in Human Postextraction Tooth Sockets.

Asparuhova, Maria B; Riedwyl, Dominic Nils; Aizawa, Ryo; Raabe, Clemens; Couso-Queiruga, Emilio; Chappuis, Vivianne (2023). Local Concentrations of TGF-β1 and IGF-1 Appear Determinant in Regulating Bone Regeneration in Human Postextraction Tooth Sockets. International journal of molecular sciences, 24(9) MDPI 10.3390/ijms24098239

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Healing after tooth extraction involves a series of reparative processes affecting both alveolar bone and soft tissues. The aim of the present study was to investigate whether activation of molecular signals during the healing process confers a regenerative advantage to the extraction socket soft tissue (ESsT) at 8 weeks of healing. Compared to subepithelial connective tissue graft (CTG), qRT-PCR analyses revealed a dramatic enrichment of the ESsT in osteogenic differentiation markers. However, ESsT and CTG shared characteristics of nonspecialized soft connective tissue by expressing comparable levels of genes encoding abundant extracellular matrix (ECM) proteins. Genes encoding the transforming growth factor-β1 (TGF-β1) and its receptors were strongly enriched in the CTG, whereas the transcript for the insulin-like growth factor-1 (IGF-1) showed significantly high and comparable expression in both tissues. Mechanical stimulation, by the means of cyclic strain or matrix stiffness applied to primary ESsT cells (ESsT-C) and CTG fibroblasts (CTG-F) extracted from the tissue samples, revealed that stress-induced TGF-β1 not exceeding 2.3 ng/mL, as measured by ELISA, in combination with IGF-1 up to 2.5 ng/mL was able to induce the osteogenic potential of ESsT-Cs. However, stiff matrices (50 kPa), upregulating the TGF-β1 expression up to 6.6 ng/mL, caused downregulation of osteogenic gene expression in the ESsT-Cs. In CTG-Fs, endogenous or stress-induced TGF-β1 ≥ 4.6 ng/mL was likely responsible for the complete lack of osteogenesis. Treatment of ESsT-Cs with TGF-β1 and IGF-1 proved that, at specific concentrations, the two growth factors exhibited either an inductive-synergistic or a suppressive activity, thus determining the osteogenic and mineralization potential of ESsT-Cs. Taken together, our data strongly warrant the clinical exploration of ESsT as a graft in augmentative procedures during dental implant placement surgeries.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > School of Dental Medicine > Department of Oral Surgery and Stomatology
04 Faculty of Medicine > School of Dental Medicine > Oral Surgery Research

UniBE Contributor:

Asparuhova, Mariya Bozhidarova, Riedwyl, Dominic Nils, Aizawa, Ryo, Raabe, Clemens, Couso-Queiruga, Emilio, Chappuis, Vivianne


600 Technology > 610 Medicine & health








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Date Deposited:

15 May 2023 12:38

Last Modified:

16 May 2023 15:43

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Uncontrolled Keywords:

bone and soft tissue augmentation connective tissue grafts cyclic strain extracellular matrix proteins growth factors implant placement matrix stiffness osteogenesis transcription wound healing





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