细胞生物学
运行x2
成骨细胞
MAPK/ERK通路
化学
碱性磷酸酶
信号转导
破骨细胞
细胞分化
骨吸收
间充质干细胞
p38丝裂原活化蛋白激酶
内科学
内分泌学
生物
医学
生物化学
体外
酶
基因
作者
Toshihiro Inubushi,Azuma Kosai,Shyunryo Yanagisawa,Chanbora Chea,Mutsumi Miyauchi,Satoshi Yamasaki,Eiji Sugiyama,Atsushi Ishikado,Tomoki Makino,Takashi Takata
标识
DOI:10.1016/j.job.2020.05.001
摘要
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.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.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.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.
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