Bone Morphogenetic Protein-2 Promotes Osteoclasts-mediated Osteolysis via Smad1 and p65 Signaling Pathways
| Autor: | Jiabin Yuan, Jingfeng Li, Xiaoming Li, Fei Wang, Jinhui Wu, Shu Liu, Weina Zheng, Jiaoyang Zheng, Chao Wang, Zhicai Shi, Xiong Miao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Osteolysis
Bone Morphogenetic Protein 2 Osteoclasts Bone morphogenetic protein 2 Bone resorption Smad1 Protein Mice 03 medical and health sciences 0302 clinical medicine Osteoclast medicine Animals Humans Orthopedics and Sports Medicine Cells Cultured 030222 orthopedics biology business.industry Macrophages NF-kappa B Cell Differentiation medicine.disease Coculture Techniques Cell biology Mice Inbred C57BL IκBα HEK293 Cells medicine.anatomical_structure RANKL biology.protein Phosphorylation Neurology (clinical) Signal transduction business 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Spine. 46:E234-E242 |
| ISSN: | 1528-1159 0362-2436 |
| Popis: | Study design An in vitro biological study. Objective The aim of this study was to explore the role of bone morphogenetic protein-2 (BMP-2) in the regulation of osteoclast-mediated osteolysis, and the possible mechanism involving BMP-2 and nuclear factor-kappa B (NF-κB) signaling pathways. Summary of background data Recombinant human BMP-2 (rhBMP-2) has been approved as a therapeutic agent in spinal fusion and bone defect repair. However, its efficacy and clinical application are limited by associated complications including osteoclast-mediated bone resorption. The mechanism of BMP-2-induced osteolysis remains unknown. Methods Bone marrow-derived macrophages (BMMs) were isolated from C57BL/6J mice and cultured with macrophage colony-stimulating factor (M-CSF) and receptor activator for nuclear factor-κB Ligand (RANKL) to induce osteoclast differentiation. An in vitro bone resorption assay was performed by co-culturing BMMs and bone slides. The expression of BMP canonical and NF-κB signaling factors and their interaction during signal transduction were quantitated by reverse transcription polymerase chain reaction, Western blot analysis, confocal microscopy, and co-immunoprecipitation. Results BMP-2 enhanced osteoclast-mediated bone resorption via inducing osteoclast differentiation in a concentration-dependent manner. In addition, a high concentration of BMP-2 significant upregulated phosphorylation of BMP signaling factors p-Smad1/5/8 and NF-κB downstream factor p65, and promoted the degeneration of IκBα. In addition, BMP-2 induced osteoclast differentiation through coupling between BMP receptor II and RANK. Conclusion High concentrations of BMP-2 enhanced osteoclast-mediated bone resorption by promoting RANKL-induced pre-osteoclast differentiation, probably by mediating the cross-talk between BMP canonical and NF-κB signaling pathways.Level of Evidence: N/A. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|