Neuromedin B and its receptor silencing suppresses osteoclast generation by modulating precursor proliferation via M-CSF/c-Fms/D-type cyclins
Journal Article
·
· Experimental Cell Research
Neuromedin B (NMB), a mammalian bombesin-like peptide, regulates diverse physiological processes, such as energy metabolism, memory and fear behavior, and cellular growth, through its cognate receptor, NMBR. In this study, we report that NMB expression was upregulated during osteoclast development and that silencing NMB or NMBR attenuated osteoclast generation mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). We found that knockdown of NMB or NMBR using a small hairpin RNA suppressed M-CSF-induced proliferation of osteoclast precursor cells without altering osteoclast differentiation. Interestingly, NMB or NMBR knockdown reduced the expression of the M-CSF receptor, c-Fms, which is an important modulator of osteoclast development. Consequently, NMB or NMBR silencing inhibited M-CSF/c-Fms-mediated downstream signaling pathways like activation of ERK and Akt and induction of D-type cyclins, cyclin D1 and D2. Moreover, knockdown of NMB or NMBR accelerated apoptosis in osteoclast lineage cells by inducing caspase-3, caspase-9, and Bim expression. In summary, our study demonstrates that the NMB/NMBR axis plays a pivotal role in osteoclast generation by modulating the proliferation and survival of osteoclast lineage cells. - Highlights: • NMB and NMBR expression is regulated during osteoclast development. • NMB/NMBR axis regulates osteoclast generation mediated by M-CSF and RANKL. • NMB/NMBR silencing suppresses M-CSF-induced osteoclast precursor proliferation. • NMB/NMBR silencing accelerates apoptosis in osteoclast lineage cells.
- OSTI ID:
- 22738164
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 359; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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