The protective effect of WKYMVm peptide on inflammatory osteolysis through regulating NF-κB and CD9/gp130/STAT3 signalling pathway

Autor: Xinyun Han, Xianghe Li, Zhengwei Yang, Lianli Duan, Li Li, Lu Hongwei, Junxian Hu, Qingyi He, Yueqi Chen
Rok vydání: 2019
Předmět:
0301 basic medicine
Lipopolysaccharides
Osteolysis
Osteoclasts
chemistry.chemical_compound
Mice
0302 clinical medicine
Osteogenesis
inflammatory osteolysis
Cytokine Receptor gp130
biology
Cell Death
Chemistry
lipopolysaccharide
NF-kappa B
Cell Differentiation
Resorption
WKYMVm peptide
medicine.anatomical_structure
RANKL
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
medicine.symptom
Oligopeptides
Signal Transduction
musculoskeletal diseases
STAT3 Transcription Factor
Osteocalcin
Inflammation
Protective Agents
Models
Biological
Bone resorption
Tetraspanin 29
Proinflammatory cytokine
03 medical and health sciences
Osteoclast
medicine
Animals
Bone Resorption
osteoclastogenesis
Macrophages
RANK Ligand
Skull
NF-κB
Cell Biology
Original Articles
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
RAW 264.7 Cells
biology.protein
Cancer research
Reactive Oxygen Species
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Popis: The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast‐related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)‐1β and TNF‐α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL‐ and lipopolysaccharide (LPS)‐induced osteoclast differentiation and maturation in vitro and alleviates LPS‐induced osteolysis in animal models. WKYMVm down‐regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF‐kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis.
Databáze: OpenAIRE
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