Bovine lactoferrin enhances osteogenesis through Smad2/3 and p38 MAPK activation
| Autor: | Azuma Kosai, Takashi Takata, Toshihiro Inubushi, Satoshi Yamasaki, Shyunryo Yanagisawa, Mutsumi Miyauchi, Eiji Sugiyama, Taketoshi Makino, Atsushi Ishikado, Chea Chanbora |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cell signaling Osteoclasts Medicine (miscellaneous) Smad2 Protein p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Bone resorption Mice 03 medical and health sciences 0302 clinical medicine Osteogenesis Osteoclast Bone cell medicine Animals Smad3 Protein Bone regeneration General Dentistry Osteoblasts Chemistry Cell Differentiation 030206 dentistry Cell biology RUNX2 Lactoferrin 030104 developmental biology medicine.anatomical_structure Signal transduction |
| Zdroj: | Journal of Oral Biosciences. 62:147-154 |
| ISSN: | 1349-0079 |
| DOI: | 10.1016/j.job.2020.05.001 |
| Popis: | Objectives Lactoferrin (LF) possesses diverse biological functions. We previously reported that bovine LF (bLF) attenuates lipopolysaccharide-induced bone resorption in osteoblasts. In addition to its ability to inhibit osteoclastogenesis, bLF has been implicated in stimulating bone formation. However, the molecular mechanisms of bLF in bone cell anabolism remain unclear. Here, we tried to analyse the molecular mechanisms involved in osteogenesis in the presence of bLF. Methods Alkaline phosphatase activity, Runx2 activity, gene expression, and Alizarin red staining were analyzed to evaluate the osteogenic differentiation status. The expression of the Smads and mitogen-activated protein kinase (MAPK) signaling molecules was analyzed via western blotting. Ex vivo organ cultures of mouse calvariae were performed to evaluate the effect of bLF on bone regeneration. Results bLF enhanced the osteoblastic differentiation of mesenchymal stem cells through activation of Smad2/3 and p38 MAPK, which increased the transcriptional activity of Runx2. bLF treatment also enhanced osteoblastic differentiation and mineralized nodule formation of osteoblast-lineage cells, and repaired bone defects ex vivo. Moreover, inhibition of Smad2/3 or p38 MAPK signaling reduced the anabolic effects of bLF. Together, these results suggested that bLF is a potent osteogenic factor, which mediates its function via activation of the Smad2/3 and p38 MAPK signaling pathways. Conclusions Here, we described a novel function of bLF and its signal transduction mechanisms in osseous tissue. Along with inhibiting osteoclastogenesis, bLF may limit further osteoclast formation and contribute to bone mass enlargement. Thus, bLF represents a potentially valuable therapeutic agent for bone regeneration and destructive bone diseases. |
| Databáze: | OpenAIRE |
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