Influence of leptin and compression in GAS-6 mediated homeostasis of periodontal ligament cell

Growth arrest-specific protein 6 (GAS-6) regulates immunomodulatory and inflammatory mechanisms in periodontium and may participate in obesity predisposition. This study aimed to determine whether GAS-6 is associated with the homeostasis of periodontal ligament (SV-PDL) cells in the presence of adipokines or compressive forces. The SV-PDL cell line was used. Western blots were employed for TAM receptors detection. Cells were stimulated using different concentrations of GAS-6. The migration, viability, and proliferation were measured by a standard scratch test, MTS assay, and immunofluorescent staining. The mRNA expression was analyzed by RT-PCR. Release of TGF-beta 1, GAS-6, and Axl were verified by ELISA. Western blot shows that TAM receptors are expressed in SV-PDL cells. GAS-6 has a promoting effect on cell migration and proliferation. RT-PCR analysis showed that GAS-6 induces Collagen-1, Collagen-3, Periostin, and TGF-beta 1 mRNA expression whereas it reduces Caspase-3, Caspase-8, Caspase-9, and IL-6 mRNA expression. Further, secreted GAS-6 in SV-PDL is reduced in response to both compressive forces and leptin and upregulated by IL-6. Additionally, ADAM-10 inhibition reduces GAS-6 and Axl release on SV-PDL cells. TAM receptors especially Axl are identified as the receptors of GAS-6. GAS-6/TAM interactions contribute to periodontal ligament cells homeostasis. Leptin inhibits the GAS-6 release independently of ADAM-10 metalloprotease.

Automated summary

GAS-6 plays a promoting role in the homeostasis of periodontal ligament cells, and is associated with leptin and compressive forces. GAS-6 induces cell migration and proliferation, and regulates the expression of multiple genes.