Functional modulation of lysophosphatidic acid type 2 G-protein coupled receptor facilitates alveolar bone formation.

Abstract

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG-35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type-specific responses, with AMG-35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG-35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF-β1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG-35 elicits osteoblast differentiation through TGF-β1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-β1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG-35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.

• Authors: Tae-Young Kim, Anna Kim, Yam Prasad Aryal, Shijin Sung, Elina Pokharel, Sanjiv Neupane, So-Young Choi, Jung-Hong Ha, Jae-Kwang Jung, Hitoshi Yamamoto, Chang-Hyeon An, Jo-Young Suh, Wern-Joo Sohn, Youngkyun Lee, Il-Ho Jang, Derek D Norman, Gabor J Tigyi, Seo-Young An, Jae-Young Kim
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 239 Issue 1 Pg. 112-123 (Jan 2024) ISSN: 1097-4652 [Electronic] United States
• PMID: 38149778 (Publication Type: Journal Article)
• Copyright: © 2023 Wiley Periodicals LLC.

Chemical References

• lysophosphatidic acid
• Lysophospholipids
• Transforming Growth Factor beta1
• Receptors, Lysophospholipid

Topics

• Animals
• Mice
• Cell Differentiation (physiology)
• Lysophospholipids (metabolism)
• Osteoblasts (metabolism)
• Osteogenesis
• Periodontal Ligament (metabolism)
• Tooth Loss
• Transforming Growth Factor beta1 (metabolism)
• Receptors, Lysophospholipid (metabolism)