Pentraxin 3 promotes the osteoblastic differentiation of MC3T3-E1 cells through the PI3K/Akt signaling pathway

Yong Liu,Hui Wang,Xiao-Zhe Zhou,Tao-Ping Chen,Yi-Chao Guo,Ning Li

doi:10.1042/bsr20201165

Abstract

Osteoblast cells are responsible for synthesizing new bone tissue, and determining how to control osteoblastic differentiation is vital to the treatment of osteoporosis. In the present study, we show that pentraxin 3 (PTX3) signaling is involved in the regulation of osteoblastic differentiation in MC3T3-E1 cells. Our data reveal that PTX3 is abundantly expressed in MC3T3-E1 cells and that its expression is inducible by the introduction of osteogenic induction medium (OIM). Overexpression of PTX3 was observed to significantly increase the expression of four osteoblast signature genes, including Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN) and osterix (OSX), suggesting that the overexpression of PTX3 promotes osteoblastic differentiation. The relative level of gene expression between OIM and OIM plus overexpressed PTX3 was evaluated using the Affymetrix Gene Chip® mouse gene microarray. PTX3-related differentially expressed genes (DEGs) were screened. Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analyses were performed, and the PI3K/Akt signaling pathway was primarily involved in the osteogenic differentiation of PTX3. Protein–protein interactions (PPIs) were also constructed, and the molecular complex detection (MCODE) plugin calculated modules of PPI networks. Moreover, we show that the effect of PTX3 is mediated by its induction of the PI3K/Akt signaling pathway. Mechanistically, we show that the action of PTX3 requires the activation of PI3K and Akt, and deactivation of PI3K by its inhibitor LY294002 weakens the PTX3-mediated induction of osteoblast signature genes, ALP and matrix mineralization. The present study revealed a new role played by PTX3 and suggest a potential mechanism governing the osteoblastic differentiation of MC3T3-E1 cells.

Highlights

Osteoporosis is a condition in which bone becomes weak and is characterized by low bone mass and structural deterioration [1,2]
Compared with the osteogenic induction medium (OIM) group, the promotion of the effects of pentraxin 3 (PTX3) on the expression of Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), OCN and OSX was attenuated by pretreatment with LY294002 (Figure 4C). These results indicate that the PI3K/Akt signaling pathway plays an important role in the effects of PTX3 on the osteogenic differentiation of MC3T3-E1 cells
Osteoblasts are bone-building cells, and the fine regulation of osteogenic differentiation is critical to the process of bone formation, modeling, and remodeling

Summary

Introduction

Osteoporosis is a condition in which bone becomes weak and is characterized by low bone mass and structural deterioration [1,2]. Bone tissue becomes fragile and shows increased vulnerability to fracture. Osteoporosis affects approximately 200 million people and is often unrecognized until one encounters the fracture due to the silent nature of the disease [3]. Bone is maintained by the constant process of bone remodeling [4]. Osteoblasts are generated from the osteogenic differentiation of mesenchymal stem cells (MSCs). MSCs possess the capacity to self-renew and differentiate into multiple cell types. It is known that MSCs are common precursors for osteoblasts [5]. The direction of MSC differentiation depends on License 4.0 (CC BY)

Methods

Results

Conclusion