trp-lys-tyr-met-val-met and Osteolysis

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.

Topics: Animals; Bone Resorption; Cell Death; Cell Differentiation; Cytokine Receptor gp130; Inflammation; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Models, Biological; NF-kappa B; Oligopeptides; Osteocalcin; Osteoclasts; Osteogenesis; Osteolysis; Protective Agents; RANK Ligand; RAW 264.7 Cells; Reactive Oxygen Species; Signal Transduction; Skull; STAT3 Transcription Factor; Tetraspanin 29