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Research Paper|Volume 14, Issue 23|pp 9445—9457

Ganglioside GD1a enhances osteogenesis by activating ERK1/2 in mesenchymal stem cells of Lmna mutant mice

Dong Hoon Kwak1,2, Ji Hye Park1,2, Eul Sig Choi1,2, Seong Hyun Park1,2, Seo-Yeon Lee1,2, Seoul Lee1,2
  • 1Department of Pharmacology, School of Medicine, Wonkwang University, Iksan, Jeollabuk-do 54538, Republic of Korea
  • 2Brain Research Institute, Wonkwang University, Iksan, Jeollabuk-do 54538, Republic of Korea
Received: September 30, 2022Accepted: October 24, 2022Published: November 14, 2022
https://doi.org/10.18632/aging.204378

Copyright: © 2022 Kwak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mutations in Lmna usually cause a series of human disorders, such as premature aging syndrome (progeria) involving the skeletal system. Gangliosides are known to be involved in cell surface differentiation and proliferation of stem cells. However, the role of gangliosides in Lmna dysfunctional mesenchymal stem cells (MSCs) is unclear. Therefore, Ganglioside's role in osteogenesis of Lmna dysfunctional MSCs analyzed. As a result of the analysis, it was confirmed that the expression of ganglioside GD1a was significantly reduced in MSCs derived from LmnaDhe/+ mice and in MSCs subjected to Lamin A/C knockdown using siRNA. Osteogenesis-related bone morphogenetic protein-2 and Osteocalcin protein, and gene expression were significantly decreased due to Lmna dysfunction. A result of treating MSCs with Lmna dysfunction with ganglioside GD1a (3 μg/ml), significantly increased bone differentiation in ganglioside GD1a treatment to Lmna-mutated MSCs. In addition, the level of pERK1/2, related to bone differentiation mechanisms was significantly increased. Ganglioside GD1a was treated to Congenital progeria LmnaDhe/+ mice. As a result, femur bone volume in ganglioside GD1a-treated LmnaDhe/+ mice was more significantly increased than in the LmnaDhe/+ mice. Therefore, it was confirmed that the ganglioside GD1a plays an important role in enhancing osteogenic differentiation in MSC was a dysfunction of Lmna.