The effects of vasoactive intestinal peptide on RANKL-induced osteoclast formation
| Autor: | Zuohui Zhao, Yan Zhuang, Kelai Wang, Hong-Yi Qu, Lin Zhu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine MAPK/ERK pathway medicine.medical_specialty 030102 biochemistry & molecular biology biology Chemistry Vasoactive intestinal peptide Osteoblast General Medicine Bone resorption Bone remodeling 03 medical and health sciences 030104 developmental biology Endocrinology medicine.anatomical_structure Osteoprotegerin Osteoclast RANKL Internal medicine medicine biology.protein Original Article |
| Zdroj: | Ann Transl Med |
| ISSN: | 2305-5847 2305-5839 |
| DOI: | 10.21037/atm-20-7607 |
| Popis: | Background Congenital pseudarthrosis of the tibia is a rare disease characterized by an imbalance in bone remodeling. Vasoactive intestinal peptide (VIP) has been proven to modulate bone resorption and the formation of osteoclasts. This study aimed to explore the effects of VIP on the homeostasis of bone metabolism in diverse in vitro systems. Methods Bone marrow-derived macrophages (BMMs) were differentiated into tartrate-resistant acid phosphatase-positive cells through incubation with receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). In vitro resorption pit detection was carried out to assess the effects of VIP on osteoclastic activity. Rat osteosarcoma cell line ROS 17/2.8 was cultured alone or co-cultured with rat BMMs in the presence or absence of VIP at various concentrations. The expression levels of RANKL, RANK, OPG, NF-κB, IL-6, ERK, CAII, and GAPDH were determined by qRT-PCR and WB assay. Results VIP was observed to repress osteoclast differentiation without affecting the number of osteoclast precursor cells. Furthermore, the modulation of the RANKL/osteoprotegerin (OPG), nuclear factor-κB (NF-κB), and extracellular signal-regulated kinase (ERK) signaling pathways were involved in the inhibitive influence of VIP upon bone erosion. Additionally, VIP affected the expression levels of osteoclastic factors including RANKL, OPG, and interleukin-6 in osteoblast cells. Furthermore, the expression levels of RANKL and RANK were increased, while OPG expression was reduced after treatment with VIP in the co-culture of ROS 17/2.8 and rat BMMs. ERK and NF-κB signal pathways were demonstrated to be involved in the effect of VIP in the co-culture system. Conclusions VIP plays a critical role in bone remodeling and might serve as a potential target in the development of treatments for congenital pseudarthrosis of the tibia. |
| Databáze: | OpenAIRE |
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